LaLiga chiefs rejected a request from Barcelona to postpone the match in light of violent scenes that marred Sunday's vote and left 465 people injured according to the Catalan health ministry, after the referendum was declared to be unconstitutional by the country's national government
Barcelona president Josep Maria Bartomeu explained the decision to play at an empty Camp Nou was borne out of solidarity and a "rejection of what has been experienced" as the stadium scoreboard bore the message "Democracia", featuring an illustration of a ballot box.
But a home side featuring five Catalans were seemingly unsettled by the circumstances and their surroundings during a listless first-half showing. Las Palmas enjoyed the greater share of possession and hit the post through Jonathan Calleri, with Barca's only advantage appearing in a 4-0 yellow card count at the break.
The half-time introduction of Ivan Rakitic and Andres Iniesta by Ernesto Valverde proved inspired as their midfield colleague Busquets – one of the Catalan contingent - crowned Barcelona's most convincing passage of play by breaking the deadlock in the 49th minute.
Messi then came to the fore in typical style with a brace inside the final 20 minutes to increase Barcelona's advantage over Real Madrid to 10 points before their rivals host Espanyol later on Sunday, although a late injury to Iniesta took some shine off the win.
Barca came out for kick-off in their cavernous surroundings wearing shirts bearing the red and yellow stripes of the Catalan flag, removing them before kick-off to unveil Barca's traditional red and blue – avoiding a clash with Las Palmas' canary kits.
The visitors' jerseys were embroidered with the date and the Spanish flag, a move announced in a statement earlier on Sunday by Las Palmas in opposition to Catalan separatism.
Sergi Roberto, Barcelona's Spain international who has also played for Catalonia's representative side, had the first attempt of the match – Leandro Chichizola in the Las Palmas goal holding a low drive.
The surreal nature of the occasion appeared to stifle both teams in the early exchanges before Chichizola pawed a Messi free-kick away from his top corner and got up sharply to deny Luis Suarez on the rebound.
Calleri thudded a shot against of the post following a 43rd-minute cutback from the excellent Oussama Tannane and Barcelona's frustration was underlined by Busquets and Jordi Alba collecting bookings for dissent in the closing moments of the first half.
Valverde turned to Rakitic and Iniesta at the restart and the midfield duo instantly lifted the flagging hosts.
Chichizola kept out another Messi free-kick and pushed Rakitic's dipping effort over the bar, although he was culpable from the resulting corner – coming out to his near post as Busquets got there first and headed in.
The goalkeeper got back on track by thwarting Messi again shortly afterwards and Luis Suarez was booked for simulation in the 52nd minute, going over under Chichizola's challenge when it appeared easier to score.
Unperturbed, the Uruguayan then darted in behind the Las Palmas defence to cause havoc in the area, although Messi planted a header wide from his eventual cross.
The five-time Ballon d'Or winner seemed to be looking at a fruitless outing as another attempt was deflected past the post but he classily made the points safe.
Denis Suarez's 70th-minute throughball was inch perfect and Messi majestically danced around Chichizola to net a 10th LaLiga goal of the season.
There was more to come from Messi as he continued a darting run for Rakitic and Luis Suarez to work possession back to him for a trademark finish 13 minutes from time – another inevitable moment of brilliance from Barcelona's talisman on a day where his on-field heroics were forced to take a backseat in this football-mad city.
