Pickering stayed close early, but DeQuincy went on a big run in the second half to pull away.
The Red Devils went scoreless in the second half as they fell 42-14 Friday night on the road.
"I really thought we played well in the first half," Pickering head coach Ryan Russo said. "The defense played together, hustled to the ball and tackled well. We've been waiting on that. (Marlon Freeney) came in as a freshman in a backup quarterback role in a big time district game and executed the offense. We played pretty well early on."
Injuries have started to pile up for Pickering, leading to players in different positions and guys missing time.
"We just have to keep developing the kids that are next in line," Russo said. "When they get thrown out there, they get better and better. Christopher Wooten is a good example of that. A few weeks ago, he had to come in for Richard Trotter, and he's only gotten better as the weeks have went on. That's what you have to do at every position.
"(Offensive coordinator) Logan Morrison had five or six guys out of position to make up for the guys we didn't have in the lineup."
Pickering took an early 7-0 on a 5-yard run by Freeney, who is filling in for Braden Lebato at quarterback.
After a DeQuincy score, Pickering running back Deon Street ran in a 3-yard touchdown to extend the lead to 14-6 in the second quarter.
The Red Devils recovered the ensuing onside kick but could not punch it in.
"We had a good chance to go up two touchdowns, but a penalty set us back," Russo said. "Until a targeting call on (running back) Greg Jones late in the second quarter, I thought we really controlled the line of scrimmage on both sides and were playing really well. We had momentum, and it would have been nice to withstand the injuries and see how we could finish that game."
Following the Street score, the Tigers took over, scoring 36 straight points and forcing four Pickering turnovers.
"There was no quit in the guys," Russo said. "We battled until the end. You have a backup in there, and if he goes down with cramps, you have the backup to the backup in there. A good team like DeQuincy is going to find that and expose it. That's just what happened. We got worn down.
Anthony Woods led the Red Devils with 81 yards on 12 carries, and Street put up 50 yards on four carries.