In 2009, Liss-Riordan co-founded the firm Lichten & Liss-Riordan, where she has filed suits against a number of tech companies in the "gig economy", including FedEx, Lyft, Uber and Amazon. Other suits were filed against GrubHub, Doordash, Square, Inc., Caviar, PostMates, Shyp, Washio, Handy, Homejoy, and InstaCart. Many of these cases involved the question of whether the companies improperly classified their workers as independent contractors. She has also filed labor suits alleging tips, fees, or wages were improperly taken from workers at restaurants, strip clubs, American Airlines, and Starbucks. In 2015, the Wall Street Journal called her "one of the most influential—and controversial—figures in Silicon Valley." Politico included her in 2016 on the "Politico 50" which is list ofthe people who are "transforming American politics." Liss-Riordan is best known for leading a class action case on behalf of Massachusetts and California drivers against ride-sharing company Uber, filed in 2013 and known as O'Connor v. Uber. The case argued that Uber drivers were misclassified as independent contractors, which the company had done to avoid giving the drivers employer-sponsored benefits and insurance. In 2016, Liss-Riordan advocated for a controversial settlement estimated totaling up to $100 million; when nine different attorneys representing drivers argued against the deal, Liss-Riordan filed to reduce her firm's fee by $10 million for the proposed settlement. About thirty drivers filed objections to the settlement or sought to remove Liss-Riordan as the leader of the class action lawsuits. A final settlement for $20 million in 2019 covered 13,600 drivers, after an appeals court ruling reduced the class from the 385,000 drivers covered by Liss-Riordan's original filing. She later defended her choice to settle the case, after some drivers were dissatisfied with still being classified as independent contractors.
2020 U.S. Senate campaign
On May 20, 2019, Liss-Riordan announced that she was running for the United States Senate for Massachusetts as a Democrat in the 2020 election. She told journalist Jim Braude that she was inspired by Representative Ayanna Pressley's win against an incumbent congressman. Liss-Riordan reported raising $1.1 million by the Federal Election Commission deadline on June 30, 2019, which included a $1 million personal loan from Liss-Riordan and $145,481 in individual contributions. On January 17, 2020, she withdrew from the race.