The 26-year-old Paraguay forward netted for the tenth time this season six minutes before the half-time break.
He then made sure Dortmund took three points at home when his shot took a deflection off St Pauli defender Ralph Gunesch on the way into the net on 49 minutes for an own goal.
Meanwhile Egyptian striker Mohamed Zidan couldn't feature in this game after picking up an injury last week. However he is expected to be fit for Dortmund's next game against Bayern Munich next Saturday.
Second-placed Bayer Leverkusen play relegation-threatened Stuttgart on Sunday hoping to bridge the gap behind the league leaders, who are on course for their first league title since 2002.
Leverkusen are still without ex-Germany captain Michael Ballack, who is expected to start on the bench after picking up a knee injury recently.
Hanover are back up to third in the table after their 3-0 win over Kaiserslautern as former Germany striker Jan Schlaudraff netted twice.
Defending champions Bayern Munich dropped to fourth after Hanover's win, but the Bavarians have the chance to regain third if they beat fifth-placed Mainz on Saturday evening.
Hamburg coach Armin Veh left Dutch hot-shot Ruud van Nistelrooy on the bench for his side's 4-0 win over Werder Bremen on Saturday.
Van Nistelrooy has been unsettled in the Hanseatic city since former club Real Madrid tried to lure him back to Spain in January.
In the Dutchman's absence, Peru striker Jose Guerrero netted twice as Werder Bremen remain just a point above the bottom three while Hamburg are seventh.
Freiburg's Senegal striker Papiss Demba Cisse netted his 16th goal in 21 league games this season with a superb strike as he held off several defenders before stabbing the ball home on 70 minutes to seal a 2-1 win over Wolfsburg.
The defeat leaves Wolfsburg just a point above a relegation place as they lost again after sacking ex-England coach Steve McClaren a fortnight ago.
Cologne continue to pick up points and showed their fighting spirit with a 1-1 draw against Hoffenheim.
Nuremberg are up to eighth in the Bundesliga after their impressive 3-0 victory, their fourth straight win, against Eintracht Frankfurt on Friday night.
On Sunday, bottom side Borussia Moenchengladbach host Schalke 04, who drew 1-1 with Valencia in Spain in the last 16 of the Champions League in midweek.