Messi's goalscoring love affair with Sevilla continued at the Ramon Sanchez Pizjuan stadium as he has now scored more goals against them than any other team - 36 in 35 matches, including what is now three hat-tricks.
Luis Suarez made it four with a fantastic lob over an on-rushing Vaclik off an assist from Messi in added time as Barca move eight points clear of second-place Atletico Madrid.
It is also a new La Liga record for most goals against an opponent, taking his tally to 28 against Sevilla, pulling away from a tie with former Real Madrid star Cristiano Ronaldo, who had netted 25, also against Sevilla.
Gerard Pique questioned Santiago Solari complaints about the fixture schedule after the Real Madrid coach asked why Barcelona will have an extra day to prepare for Wednesday's Clasico, noting extra rest did not help Los Blancos when the clubs clashed in October. Therefore, they need to be in top form as these matches will go a long way to defining their season.
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"We went through a spell where, to be honest, we did not play our best football so that made it much harder for us to score".
Though Gabriel Mercado had the hosts back in front just before the break, Messi again replied in the second half, levelling in the 67th minute before sealing his hat-trick with a stunning volley five minutes from time.
There, they had thrashed Real Madrid 3-0 and beaten Barca 2-0 in the Copa del Rey this season. "His stats this season are 12 goals from 30 appearances, he is performing, yet he is still the whipping boy", Berbatov told Betfair. "We were having trouble converting our chances", Messi said.
Barca's games in La Liga and the Champions League can be viewed on fuboTV (Try for free).
"We will have three really tough games in seven days, so we'll have to think about rotating".