Selby followed Neil Robertson, Ding Junhui and Stuart Bingham out of the exit door after a below par performance against world number 36 Gilbert.
Gilbert won the first frame by potting the final pink and black, and never looked back as he won the last three with top breaks of 50 and 73. Tamworth's Gilbert now faces Joe Perry with the chance to reach the quarter-finals of a ranking event for the first time - though he did get to the semis of the Rotterdam Open European Tour event last July which earned him a spot in Preston.
"It's a great result for me although I was lucky tonight because Mark was struggling," admitted Gilbert. "For the last few months I have been playing dreadful but hopefully this will give me a bit of confidence.
"I was a bit nervous in the first frame but only because I've been playing rubbish. I've played Joe a couple of times this season and he's beaten me so it would be nice to get one over on him."
Barry Hawkins impressed in a 4-0 win over Stephen Maguire, making top breaks of 94 and 95.
"I'm delighted because I haven't got a good record against Stephen and he is a proven winner," said Hawkins, who got to the semi-finals of the Welsh Open. "I put him under pressure and didn't miss much. I enjoy playing in front of the TV cameras."
Joe Perry edged out Mark Davis 4-3, knocking in runs of 70, 86, 123 and a crucial 75 in the decider.
Fergal O'Brien beat Michael Holt 4-3, getting the better of a deciding frame which finished at 12.40am.
