Game in crackers is a puzzle (6)
I believe the answer is:
enigma
'a puzzle' is the definition.
(thesaurus)
'game in crackers' is the wordplay.
'crackers' is an anagram indicator (informal term for mad).
'game'+'in'='gamein'
'gamein' is an anagram of 'ENIGMA'.
'is' is the link.
(Other definitions for enigma that I've seen before include "Mysteriously puzzling person or thing" , "'Puzzle, riddle (6)'" , "Solution to mystery" , "Gamine being a bit of a puzzle" , "WW2 code" .)