Saints boss Nigel Adkins made 10 changes to the side which swept to the top of the Championship at the weekend, but he kept Lallana in reserve just in case.
And the England Under-21 international found the net barely a minute after entering the fray to send League One Preston tumbling out and earn Saints a 15th successive home victory.
The hosts went ahead in the 27th minute when Preston failed to deal with a far-post corner from Lee Holmes.
Teenager Ben Reeves headed back across goal and Dutch centre-half Jos Hooiveld, who is on loan from Celtic, reacted first in the six-yard box to tuck the loose ball home.
Hooiveld had clearly got a taste for goalscoring as moments later he brought the ball out from the back with a 25-yard run before rifling in a shot which North End goalkeeper Andreas Arestidou held low down.
Reeves also appeared to be enjoying himself on his debut and was unlucky to see a 20-yard drive deflected wide.
The nearest Preston came to finding the net in the first half came in stoppage time when a free-kick from Steven Smith was tipped over by back-up Saints keeper Bartosz Bialkowski.
But they came up with a shock leveller six minutes after the interval when Bialkowski could only parry a shot from Darel Russell and Adam Barton squeezed in the rebound.
But Adkins turned to Lallana in the 66th minute, and the move paid immediate dividends.
With his first touch, the newcomer pushed the ball out to Holmes and then raced into the area to get on the end of the winger's cross at the near post and head in the winner.
