Several matches between the two clubs during the combative Mourinho's stint in Spain were marred by brawling, accusations of refereeing bias and play-acting although more recent meetings have been less controversial.
"It's true that in difficult moments for the national team, when the Real-Barca matches got a little strange, he (Casillas) helped the team to move on and continue winning things like the (2012) European Championship," Del Bosque told radio station Onda Cero.
"This did not go down well and perhaps had a detrimental effect also on Iker," added the former Real coach. "He was a key figure in fostering harmony in the national team."
The tension reached a low point in August 2011 when Mourinho, who returned three months ago for a second spell at Chelsea, jabbed a finger in the eye of Barca assistant coach Tito Vilanova as fighting erupted during a Spanish Super Cup game.
Real's Spain contingent, including goalkeeper Casillas, Sergio Ramos, Xabi Alonso and Alvaro Arbeloa, appeared to fall out with Barca internationals like Xavi and Carles Puyol, prompting concern it could affect the national team's performances.
Casillas, the Real and Spain captain, sought to ease the tension by meeting Xavi and Puyol, and Del Bosque suggested this had contributed to Mourinho's decision last season to replace his skipper with Diego Lopez.
Even under new Real coach Carlo Ancelotti, Casillas has been left on the bench this season.
Barca keeper Victor Valdes has been in excellent form and may start Spain's World Cup Group I qualifier against Finland in Helsinki later on Friday.