Further fuelling the criticism, US secretary of state Mike Pompeo told Indian news site The Print on Tuesday that China's actions in Xinjiang "remind us of what happened in the 1930s in Germany."
But Beijing angrily hit back on Wednesday, saying the "so-called genocide in Xinjiang is a rumour deliberately concocted by some anti-China forces."
The sensitive region is tightly controlled by Chinese authorities, and rights groups say more than one million Uighurs have been detained in camps.
Beijing defends the camps as vocational training centres to stamp out terrorism and improve employment opportunities.
"The US senators you mentioned have always been anti-China and are keen to concoct all kinds of lies to discredit China and use them to seek their own political gains," foreign spokesman Wang Wenbin told reporters.
Wang also turned the tables on China's critics, attacking the US for the "assimilation and massacres of Native Americans in history to greatly reduce their population."
"We urge certain US politicians to respect the facts, stop fabricating lies, and stop using Xinjiang-related issues to interfere in China's internal affairs," said Wang.
A report earlier this month from the Australian Strategic Policy Institute (ASPI) think tank said the network of detention centres in Xinjiang is much bigger than previously thought, despite China's claims that many Uighurs have been released.