What's surprisingly anodyne makes one cross (7)
I believe the answer is:
annoyed
'one cross' is the definition.
(thesaurus)
'what's surprisingly anodyne' is the wordplay.
'what's surprisingly' indicates an anagram.
'anodyne' anagrammed gives 'ANNOYED'.
'makes' acts as a link.
(Other definitions for annoyed that I've seen before include "Anodyne (anag.)" , "'Irritated, impatient (7)'" , "Upset" , "Vexed, irritated" , "'Harassed, pestered (7)'" .)