Moutinho has been linked with Tottenham for the last few weeks as the London club look to replace Luka Modric, who is closing in on a move to Real Madrid.
"It will be very difficult to sign him," Villas-Boas told a press conference.
Moutinho and Villas-Boas worked together at Porto, but like many of the Portuguese club's players, the 25-year-old midfielder is thought to have a hefty release clause in his contract, in his case just over £30 million.
Spurs are likely to receive that amount of money from Modric's sale, but they are also hoping to use some of the cash to add a much-needed striker. And for that reason, Villas-Boas admits signing Moutinho is unlikely.
He added: "I have experience of Porto and it is a club that sells good products but they are expensive. It has been like that with numerous amounts of players and that is why it is very difficult."
Another target, Rennes' Yann M'Vila, is also unlikely to sign.
"He is an interesting player, but I don't think he will join Tottenham," Villas-Boas said. "The player is a player of defensive characteristics.
"We had initial interest in M'Vila but we have moved on from that one and are now looking for a more creative player."