This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages)(Learn how and when to remove this template message)
Sierra's most well-known works involve hiring laborers to complete menial tasks. These works are meant to elucidate the nature of the laborer within Capitalist society, how the laborer sells his physical labor and thus his body, political issues such as immigration and continual immigrant poverty in Capitalist countries, the nature of work in Capitalist society, and the isolation of economic classes.
He achieves this through a number of techniques that present these themes and also question the nature of the art institution. While Sierra is critical of capitalism and the institutions which support it, he is also considered a successful artist. He is aware of this contradiction when he says, "self-criticism makes you feel morally superior, and I give high society and high culture the mechanisms to unload their morality and their guilt."
Some of Sierra's most famous works have involved paying a man to live behind a brick wall for 15 days, paying Iraqi immigrants to wear protective clothing and be coated in hardening polyurethane foam as "free form" sculptures, blocking the entrance of Lisson Gallery with a metal wall on opening night, sealing the entrance of the Spanish Pavilion at the Venice Biennale, only to allow Spanish citizens in to see an exhibition of left over pieces of the previous year's exhibition. Another of his well-known projects is a room of mud in Hanover, Germany, commemorating the job-creation measure origin of the Maschsee. In 2006, he provoked controversy with his installation "245 cubic metres", a gas chamber created inside a former synagogue in Pulheim, Germany. About the Biennale piece, Sierra said, "In the context of the biennial we are all playing at national pride, and I wanted to reveal that as the principal system of every pavilion...you can't forget that the countries that participate in the Biennale are the most powerful ones in the world. I mean, there's no pavilion for Ethiopia. So the theme was already a given." About his conception of nationalism for this work, Sierra has said "A nation is actually nothing; countries don't exist. When astronauts went into space they did not see a line between France and Spain; France is not painted pink and Spain blue. They are political constructions, and what's inside a construction? Whatever you want to put there."
In 2020 Sierra invited First Nations peoples from places colonised by the British empire to donate blood for an artwork called Union Flag; the Dark Mofo festival cancelled plans to show the artwork after a backlash led by Indigenous Australian artists. 
In explanation of his work, Sierra has said, "What I do is refuse to deny the principles that underlie the creation of an object of luxury: from the watchman who sits next to a Monet for eight hours a day, to the doorman who controls who comes in, to the source of the funds used to buy the collection. I try to include all this, and therein lies the little commotion about remuneration that my pieces have caused." More specific to his questioning of art institutions and capitalism, he said "At the Kunstwerke in Berlin they criticized me because I had people sitting for four hours a day, but they didn't realize that a little further up the hallway the guard spends eight hours a day on his feet...any of the people who make those criticisms have never worked in their lives; if they think it's a horror to sit hidden in a cardboard box for four hours, they don't know what work is...And of course extreme labor relations shed much more light on how the labor system actually works." Sierra has a displayed interest in visibility and invisibility. He explains the result of his work that pursues these interests, saying "The museum watchman I paid to live for 365 hours behind a wall at P.S.1 in New York told me that no one had ever been so interested in him and that he had never met so many people. I realized that hiding something is a very effective working technique. The forgotten people want to communicate..."
- Heidenreich, Stephan (1 March 2003). "Santiago Sierra". Frieze magazine. Retrieved 8 February 2021.
- Margolles, Teresa "Santiago Sierra" BOMB Magazine, Winter 2004. Retrieved 9 August 2011
- Margolles, Teresa "Santiago Sierra", BOMB Magazine Winter, 2004. Retrieved 9 August 2011
- Searle, Adrian "Buried Alive", The Guardian 13 July 2001. Retrieved 9 August 2011
- "Santiago Sierra renuncia al nacional de artes plásticas porque el premio se utiliza en 'beneficio del Estado'" [Santiago Sierra Renounces the National for Plastic Arts Because the Award is Used in 'Benefit of the State']. El País (in Spanish). Madrid. 5 November 2010. Retrieved 21 June 2019.
- Broede Carmody, Robert Moran (23 March 2021). "Dark Mofo cancels blood-soaked flag artwork". Sydney Morning Herald.