Safin, who has said that 2009 will almost certainly be his last year on tour, outclassed Spaniard Guillermo Garcia-Lopez 7-5 6-2 6-2.
The No.26 seed's third-round opponent will be Federer, assuming that the Swiss superstar beats Russian Evgeny Korolev later on Wednesday.
Safin met Federer in an epic semifinal at Melbourne Park in 2005, with the Russian winning in five sets before going on to beat Lleyton Hewitt in the final.
Novak Djokovic's Australian Open title defence remains on track after the Serb also cruised into the third round today.
Djokovic needed just one hour and 44 minutes to defeat Frenchman Jeremy Chardy 7-5 6-1 6-3 at Rod Laver Arena.
The third seed next faces either French 28th seed Paul-Henri Mathieu or American Amer Delic on Friday for a place in the last 16.
