The two Lukes had contrasting round-of-16 matches in the evening session despite both players dominating in their afternoon matches.
Littler edged past world number 31 Krzysztof Ratajski 10-8 after hitting six 180s and averaging 97.99, even squandering a 6-2 lead during the match.
Ratajski fought back first to 6-6, then 7-7, and even 8-8 before the world champion eventually pulled away and secured victory.
Humphries fared much better with an emphatic 10-2 win over Ryan Joyce to follow on from a whitewash of Ryan Searle earlier in the day.
The current world number one averaged an impressive 101.59 and broke Joyce's throw five times.
Welshman Jonny Clayton also powered into the last eight with a 10-4 victory over Martin Schindler, while Michael Smith sealed a dominant 10-3 triumph over Dimitri Van den Bergh.
James Wade, Nathan Aspinall, Gian van Veen and Josh Rock make up the rest of the quarter-final line-up.
Evening session results:
Michael Smith 10-3 Dimitri Van den Bergh
Ryan Joyce 2-10 Luke Humphries
Nathan Aspinall 10-8 William O'Connor