Pavlyuchenkova started her 2010 season by reaching the last eight at the Brisbane International where she was defeated by Ivanovic. At the Australian Open, she lost in the second round to compatriot Svetlana Kuznetsova. She then reached her first Premier 5-level quarterfinal, at the Dubai Tennis Championships by defeating Katarina Srebotnik, Tathiana Garbin and Daniela Hantuchová. There, she fell short to defending champion Venus Williams in straight sets. She then made the third round in Indian Wells and the round of 16 in Miami, losing to Samantha Stosur and Caroline Wozniacki respectively.