After the sack of Rome in 1527 and the imprisonment of Pope Clement VII (May, 1527), Quiñones, who was distantly related to the Emperor, and was also his confidant, seemed the man best able to effect the release of the pope, and a full reconciliation between him and the emperor. He was thrice sent to the emperor for this purpose, and his efforts were crowned with success by the deliverance of Pope Clement (December, 1527), and the Treaty of Barcelona (1528) and Cambrai (1529). As these embassies rendered his effective government of the Order impossible, Quiñones renounced the generalship in December 1527, and in September of the following year he was created cardinal of the title of "S. Croce in Gerusalemme", hence his name "Cardinal of the Holy Cross". From 1530 to 1533 he was also Bishop of Coria, in Spain, and for a short time, in 1539, administrator of Acerno (Naples), but he was never Cardinal Bishop at Palestrina, as some authors assert.