Messi swooped on a loose ball to level in the 50th minute before netting a superb free kick in the 73rd minute to seal Barcelona win, which lifted them at the top of the table.
Barca are now 15 points clear of second-placed Atletico Madrid and 19 ahead of third-placed Real Madrid.
Messi was desperate for the hat-trick but an exceptional save by keeper Tono in the last-minute prevented him to do so.
Barcelona will visit AC Milan on Wednesday for the final 16 of Champions League.