The Argentinean talisman supplied the first goal for Neymar in the 17th minute before side-footing past Diego Marino to double Barca's lead 21 minutes later.
Messi's close-range finish made it 3-0 on the hour-mark and when Ivan Lopez brought down Neymar in the box after 65 minutes, Messi sealed his hat-trick.
Luis Suarez rounded off the scoring with a spectacular overhead kick which confirmed an 11th successive win for the Catalan giants - a record shared from Pep Guardiola's time in charge.
But once again, Messi took the plaudits with his latest hat-trick, putting him level with Real Madrid rival Cristiano Ronaldo.
The rout reduced Real's lead atop the table to a solitary point through 23 matches.
Defending champions Atletico Madrid are six points further back after losing 2-0 at Celta Vigo.
In a significant dent to their title defence, Diego Simeone's men struggled to get to grips with their hosts all night and Celta took a deserved lead 10 minutes after the break when Nolito converted a penalty.
Atletico were left furious because in the same move, Augusto Fernandez appeared to have handled the ball.
Fabian Orellana's clinical strike 20 minutes from the end confirmed the win for Celta, who have taken four points off the champions this season.
Valencia moved into the top four with a 1-0 win over Getafe thanks to an Alvaro Negredo penalty.
The on loan Manchester City forward stepped up with 18 minutes remaining as Valencia continued their great recent run of form which has seen them record four wins in the last five league outings.
Elsewhere, Villarreal lost for only the second time in their last 13 league games after a 2-0 defeat at Rayo Vallecano.
Both goals came in the second, with Alberto Bueno nudging home from close range and Gael Kakuta's well-timed run into the box.
Rayo are the only side other than Barcelona that Villarreal have lost to in any competition in 22 games.
