Head coach Vilanova had a cancerous tumour removed in 2011 and has missed much of this season whilst undergoing further treatment.
But he was back on the bench for Barca's thumping 5-0 victory over Mallorca at the weekend - a victory that took the club 13 points clear of Real Madrid in La Liga - and will be at the helm as Barcelona attempt to reach a sixth successive Champions League semi-final on Wednesday.
"It is so difficult when the boss, when the coach is not there," Pique told Revista ahead of this week's Champions League second leg home clash against Paris Saint-Germain, which will begin with the teams locked at 2-2.
"It's true that we started really strong and then we lost some points in the league and we lost a game in the Champions League against Milan and people started to say that maybe we were not good enough.
"It was because we were in a really strange situation and now normality is returning again. We are starting to be with the boss again. In this last two months we need to improve our level so we get to the Champions League final and win the league."
Earlier this year Vilanova spent two months in New York undergoing treatment for his condition, during which time Jordi Roura took over first-team affairs.
However Pique told Revista that the 44-year-old has been in contact with the Barcelona players throughout his illness right from the first moment he told the squad of his illness.
"We had some video conferences with him before the games, just to talk about a few things - like defence and how we have to attack.
"He was there all the time even though he was ill. To be fair, we are really proud of him because he did something incredible.
"He was ill but he kept working for us and now that he is a little bit better he is going to the games and the training, so he is helping us a lot."
Vilanova stepped up into the role of Barcelona head coach at the start of the season after his predecessor Pep Guardiola admitted that his four-year spell at the helm had left him "drained".
Former Spanish international Guardiola guarded Barca to a glut of trophies, including three La Liga titles and two Champions League crowns.
The club has high hopes of adding a domestic and European league double to that haul this season even though Pique admits that the side is playing a different brand of football under Vilanova.
"We play with the same philosophy and the same style, but if you want to keep winning you have to keep changing things because eventually all of the teams know you," he said.
"It's true that sometimes it works and sometimes it doesn't but we have to keep changing."
You can see the full length version of our Pique interview on skysports.com on Wednesday evening.