Foreign Ministry Spokeswoman Maria Zakharova told journalists the report was "a false story that does not correspond to reality" and "a fake."
The damning report released Tuesday details mass hangings at one of Syria's largest detention centres near Damascus between 2011 and 2015.
Russia has backed long-time ally President Bashar al-Assad throughout the Syrian conflict and launched a bombing campaign in support of his regime in September 2015.
"This is yet another targeted act of provocation aimed at pouring oil on the fire of the dying-down conflict within Syria," she said.
Zakharova rebuked Amnesty for publishing figures that she said were "the result of mathematical calculations on the basis of testimony of unnamed people."
"The leadership of this respected NGO should take a more serious approach to these extremely dangerous fantasies of its Lebanon subsidiary," Zakharova added.