The five-time Australian Open champion took just 57 minutes to wrap up a 6-2 6-0 victory over the Russian 14th seed on the Rod Laver Arena to set up a quarter-final against fellow American Sloane Stephens.
And Williams, who stretched her unbeaten run to 20 matches with Monday’s win, conceded that she did not expect such an easy ride.
“I was surprised,” said Williams, who hit 22 winners en route to victory. “I felt like Maria played really well. I was just trying to play well, just to keep up.
“I’m really out there just doing the best I can, just fighting for everything.
“I think with that attitude I’m just trying to stay in the tournament just to stay alive.”
Kirilenko admitted that she found it difficult to find her rhythm against the 31-year-old 15-time Grand Slam winner.
“I tried to do something special tonight, that’s why I made so many mistakes. Maybe I just had to play little bit more simple.
“We didn’t even have long points. It was really difficult to get the rhythm.”
MORE: The latest tennis news