World number one Humphries made the most of Searle's struggles with finishing, averaging 100.2 and exploiting 10 missed double attempts from his opponent.
Cool Hand Luke now faces Ryan Joyce in the next round later on Saturday evening in Minehead.
Meanwhile, Luke Littler continued his impressive form, dispatching Jermaine Wattimena 10-4.
Littler showcased was his usual self-assured style on the big stage, averaging 104 and converting 10 of his 15 double attempts for a 66.70 checkout percentage.
The 18-year-old reigning world champion will now face Krzysztof Ratajski in the next round, thanks to the tournament's random draw format.
However, the day wasn't as successful for Michael van Gerwen, who suffered a shock exit at the hands of unfancied Welshman Rob Owen.
Van Gerwen's abysmal struggles with doubles proved costly, missing his first 15 attempts and only managing to convert 8 of 34 overall.
Despite MVG managing to win six legs on the bounce in what seemed the unlikeliest of comebacks, Owen was able to stay on top during the crucial dying embers to earn arguably the biggest win of his career to date.
The 10-8 defeat marked a disappointing performance for the Dutchman, one he'll be eager to put behind him as he struggles for consistency again this season.
Results
Afternoon Session (12:45 GMT)
Dimitri Van den Bergh 10-9 Chris Dobey
Luke Littler 10-4 Jermaine Wattimena
Luke Humphries 10-0 Ryan Searle
Rob Owen 10-8 Michael van Gerwen
Josh Rock 10-9 Ross Smith
Jonny Clayton 10-7 Alan Soutar
Nathan Aspinall 10-2 Jurjen van der Velde
Rob Cross 10-9 Danny Noppert
Krzysztof Ratajski 10-8 Dave Chisnall
William O'Connor 10-3 Mensur Suljovic
Michael Smith 10-7 Madars Razma
Gian van Veen 10-7 Stephen Burton
Martin Schindler 10-9 Dylan Slevin
Ryan Joyce 10-3 Danny Lauby
James Wade 10-9 Cameron Menzies
Damon Heta 10-7 Connor Scutt
Evening Session (19:00 GMT)
Sixth Round
Main Stage
Michael Smith v Dimitri Van den Bergh
Krzysztof Ratajski v Luke Littler
Ryan Joyce v Luke Humphries
Josh Rock v Rob Cross
Stage Two
Martin Schindler v Jonny Clayton
Rob Owen v James Wade
Damon Heta v Gian van Veen
Nathan Aspinall v William O'Connor