Vilanova has replaced the highly-successful Pep Guardiola after previously serving as an assistant at the Nou Camp during the Spaniard's time in charge.
However, Mascherano insists that Vilanova must quickly adapt to his new role and accept that he is now under the spotlight at one of the biggest clubs in the world.
"Tito will now carry the pressure, until now he was a lower-profile coach and all the responsibility fell on Guardiola," the 28-year-old told AS. "Now he has to assume the main role.
"Today all the attention falls on him but he has always been an important part in the success of the team. Every one of us ought to respond in the same way."
Vilanova was previously assistant manager at Barcelona B before being promoted to the first team with Guardiola.