Reigning champions Barca lead their arch rivals by a point with two matches left and play at Champions League hopefuls Sevilla, in fourth, while Real host Athletic Bilbao, who are eighth and bidding for a Europa League berth.
Ronaldo's hat-trick against Real Mallorca on Wednesday put the Portuguese third on the La Liga scoring chart with 25, one behind team mate Gonzalo Higuain, and Argentine Messi leads on 31 after his double against Tenerife on Tuesday.
Ronaldo became the world's most expensive player when he joined Real from Manchester United for around 94 million euros at the end of last season, while Messi has been at Barca since the age of 13.
A Barca victory in Sevilla and a slip-up by Real at home to Bilbao will guarantee Pep Guardiola's side a second straight title as they won both this season's "Clasicos" and head-to-head record separates sides if they are level on points.
Barca's total of 93 from 36 matches is a record, surpassing the 92 accumulated by Real under Fabio Capello in the 1996-97 season when there were 22 teams rather than 20.
"Let's hope Sevilla can take points off them, but our fate is not in our own hands," Real coach Manuel Pellegrini said at a news conference after the 4-1 win in Mallorca.
"Our obligation is to get to 98 points and we'll see if Barca can get to 99."
In Saturday's games, which are all at 7pm GMT, Xerez host Real Zaragoza, Racing travel to Valladolid, Malaga play at Getafe and Tenerife host Almeria.
