The 17-year-old averaged 103.38 as he beat Chisnall in the last 16 of the competition, after overcoming Germany's Martin Schindler.
Littler has assumed the role of 'favourite' after Michael van Gerwen was knocked out by Mensur Suljovic earlier this week.
The draw has now opened up further, following the surprise eliminations of both Michael Smith and Gary Anderson.
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Littler was able to come back from 5-3 down to beat Schindler 10-8 in the last 32 of the UK Open, which BBC Sport describes as the 'FA Cup of darts'.
The teenager began the year by becoming the youngest World Championship finalist, before falling to defeat against world number one Luke Humphries.
Littler then claimed his first PDC senior title in January by beating Van Gerwen at the Bahrain Masters
Littler v Schindler
Schindler narrowly lost the first duel between a German darts pro and child prodigy Littler on the PDC Tour. The Strausberg native lost 8-10 to the 17-year-old runner-up in the fifth round of the UK Open on Saturday, missing out on another surprise. Schindler had previously knocked the Welsh former world champion Gerwyn Price out of the tournament.
Schindler and Littler played a hard-fought match in which the German was initially on course to win after a break. But then Littler, who averaged almost 102 points, turned up the heat. Schindler held his own with a total of six 180s, but his English opponent managed to finish the match with a narrow lead.
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After a strong start, Schindler had even led 5-3 at one stage, but he ran out of steam towards the end and Littler won four legs in a row to march over the finishing line.
A total of £600,000 in prize money will be paid out at the major tournament. The defending champion is last year's surprise winner Andrew Gilding.