The world number one has steamrollered her way through the draw at Roland Garros so far, and even though Roberta Vinci gave a decent account of herself on Sunday, she still only won four games.
Williams' 6-1 6-3 victory made it 10 games lost in four matches so far, extending her winning streak to 28 matches.
Williams and Kuznetsova, a 6-4 4-6 6-3 winner over eighth seed Angelique Kerber on Sunday, have met eight times before, with the American winning six times.
But nearly all of their matches have been close, and the only previous time they have met at Roland Garros, in the quarter-finals in 2009, Kuznetsova won before going on to lift the trophy.
Williams said: "It will be a good match. The last time we played here she won, so that will probably get her pumped up and she's on a comeback.
"She has nothing to lose but everything to gain. She also wants to do well, and she's won this tournament before.
"So it's not going to be an easy match for me. I have had some pretty tough matches this clay-court season, and I think for sure that will be another one. But it will be a good job for me to see how I go there."
Kuznetsova at her best has the power and variety to trouble Williams, especially on clay, and, unlike a lot of the American's opponents, will not be intimidated.
The Russian missed the end of last season with a knee problem but reached the quarter-finals at the Australian Open in January and has climbed back to 39th in the rankings.
She knows she has her work cut out, saying of Williams: "She's the best in the world. She's been playing unbelievable tennis.
"But I believe that I have the game, and I have good days. Let's cross fingers I will have a good day for that one.
"I just go out there and play my game. Sometimes I can be very good. Sometimes I just have bad days. I'm just a human being, maybe even more than other people."
Kuznetsova shied away from comparisons with 2009 just yet, saying: "I think it's too far ahead still, but it's always great memories to play here, and it's a pleasure.
"It doesn't even matter about the memories. I always love to play in Paris. It always brings the best out of me and feels special."