The Russian star defeated Belarusian Ilya Ivashka 6-4, 6-4 in one hour and 29 minutes, marking his second win against Ivashka in St. Petersburg. Rublev saved all seven break points he faced to reach the quarter-finals at the event for the third time.
The top seed is the defending champion, and is trying to secure his third trophy on home soil after an opening-round loss last week in Moscow. He triumphed in St. Petersburg in 2020 and Moscow in 2019.
Ivashka is a dangerous player, whose aggressive game helped him claim his first tour-level crown in August in Winston-Salem. But Rublev was strong on serve, hitting 10 aces and winning 84 per cent of his first-serve points.
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On the same half of the draw, Russian Karen Khachanov and Croatian Marin Cilic set an intriguing second-round clash. Sixth-seeded Khachanov blasted through French lefty Adrian Mannarino 6-3, 6-3 in one hour and 25 minutes.
The home favourite has advanced to the quarter-finals just once in St. Petersburg, and he will attempt to do so again when he plays Cilic. The former World No. 3 is competing here for the first time since 2011, when he won the title.
Cilic defeated Spaniard Albert Ramos-Vinolas 6-2, 6-3 in one hour and 23 minutes. He carries a 1-0 ATP Head2Head edge over Khachanov into their meeting.