This paper aims to show how the Vatican’s attitude towards the Palestinian Question changed during the pontificate of Pius XI. To answer this question, it deals with four main issues: the Holy See’s attitude towards Zionism and the perspective of a Jewish State in the Christian ‘Holy Land’; the opposite claims of the Arab-Palestinian national movement; the British rule in the region; the role of the Catholic powers and their effort to use religious aspects to reinforce their policies. Regarding these last three issues, the Vatican’s attitude profoundly changed during this period. The Holy See became more positive towards the British mandate, which started to be considered as a guarantee for the Catholic presence. At the same time, the Vatican became sceptical towards the Arab nationalism, which it initially had supported, showing increasing scepticism towards the activism of the European Catholic powers in the region. In this changing picture, an element of continuity was the Catholic open hostility towards Zionism and its goals, which became only a little more moderate during the period taken into consideration.