Mascherano has been strongly linked with a return to the Premier League, with his former club Liverpool, Arsenal and Manchester United reportedly keen to acquire the 29-year-old's services.
The Argentina international, who can also operate in the centre of defence, is under contract until 2016 and a buy-out clause set at 100million euros.
"(Rafa) Benitez knows Mascherano well and esteems him," De Laurentiis said in quotes reported by Gazzetta dello Sport. "We are working on it but it's a difficult negotiation.
"In any case, the player will turn 32 in two years' time."
Benitez coached Mascherano during the player's three-year spell at Liverpool.
De Laurentiis, whose side finished third in Serie A to earn a spot in next season's UEFA Champions League qualifying round, insists his club does not want to sell Valon Behrami.
The Swiss midfielder started in just 16 league games for Napoli this season and has been linked with Tottenham.
"Right now no one is leaving," De Laurentiis said. "But it's not a case that our Champions League destiny depends only on him.
"We have a strong roster and we don't have that many positions to fill. Hence, we will have to work with a fine eye to choose the right men.
"We changed 12 players this year and the team has ended the campaign on a high, achieving a club record 104 goals.
"This means that we already have an important foundation. We have planned with Benitez the future and made a list of possible signings."