The 63-year-old actor stars alongside Melissa McCarthy, Chris O'Dowd and Naomi Watts in Ted Melfi's comedy, reported Ace Showbiz.
The film centres around Vincent, an ageing and broke bachelor whose antagonistic behaviour has left him alone in the world.
When a new neighbour (McCarthy) moves in next door, he forms an unlikely bond with her young son (Jaeden Lieberher).
Murray was most recently seen in 'The Grand Budapest Hotel' and 'The Monuments Men'. He will not be returning for the planned 'Ghostbusters' sequel.
'St Vincent' will be released in the US on October 24.