A guide is key to crossing river from the South (6)
I believe the answer is:
escort
'a guide' is the definition.
(I've seen this before)
'key to crossing river from the south' is the wordplay.
'key' becomes 'esc' ('Escape' key on a computer keyboard).
'crossing' indicates putting letters inside.
'river' becomes 'r'.
'from the south' is a reversal indicator (in a down clue, letters go up).
'to' going around 'r' is 'tro'.
'tro' reversed gives 'ort'.
'esc'+'ort'='ESCORT'
'is' is the link.
(Other definitions for escort that I've seen before include "Accompany, chaperon" , "One who accompanies another" , "Person who accompanies or guards another" , "restraint" , "Protective companion" .)