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The burly striker, 28, achieved the feat with a first-half brace that helped put his side 3-1 ahead at the break.
Keith Treacy and skipper Callum Davidson were also on target either side of half-time but the spirited Eagles ensured a nervous finish with goals from Andy Dorman and James Vaughan.
Yet Darren Ferguson's men, who began the day second-bottom, held on for a badly-needed victory, having previously only won once on home soil this season.
Parkin set them on their way in the 13th minute when he connected with Paul Coutts' left-wing cross and fired a right-footed shot into the bottom corner.
Palace sought to find an immediate response but Wilfried Zaha drilled a right-footed shot over the crossbar when well placed.
In the 20th minute, Palace drew level when Owen Garvan collected possession 30 yards from goal and drove an unstoppable shot into the top right-hand corner.
Yet Preston steadied themselves and regained the lead in the 25th minute when Parkin collected a pass from Sean St Ledger and drilled a right-footed shot into the top left-hand corner from 18 yards.
In a remarkably open first half, Palace could have equalised again when Dorman connected with Zaha's cross from six yards but Andy Lonergan made a fine parried save to avert the danger.
In the 29th minute, Palace went close again when Vaughan volleyed wide from 12 yards out.
However, in the 36th minute Preston claimed their third goal of the match when winger Treacy hit a spectacular shot into the top corner from 35 yards out for his sixth strike of the season.
On the stroke of half-time, Parkin twice went close to completing his hat-trick with a couple of fierce strikes that were blocked and saved.
Treacy went close to finding the net again shortly before the hour mark with a drilled effort from 18 yards which narrowly failed to find the target.
In the 66th minute, North End added their fourth goal when Julian Bennett fouled Coutts and Davidson made no mistake from the penalty spot.
To Palace's credit, they refused to surrender and Dorman hauled them back into the game in the 69th minute with his first goal for the club.
Patrick McCarthy crossed from the right flank and Dorman stooped to head the ball into the bottom left-hand corner.
With 10 minutes remaining, Darel Russell fouled Pablo Counago and Vaughan stepped up to fire home from 12 yards and set up a tense finale but Preston held on for victory.