Given the significance of cross-cultural encounters in interpretation, it seems that a key factor that can improve interpretation is the level of interpreters’ cultural intelligence (CQ) as it affects individuals’ functions in culturally diverse situations. This study aimed at exploring the association of interpreters’ CQ and their applied strategies to meet cross-cultural problems in the case of tour guide interpretation in religious contexts. A mixed methods design was employed to explore the cultural intelligence of 91 tour guide interpreters of Foreign Pilgrims’ Office of Imam Reza Holy Shrine, Mashhad, Iran. In the qualitative phase, the researchers carried out interviews with these tour guide interpreters. In this phase, the interpreters' cross-cultural problems and their strategies to tackle these problems were explored and classified. In the quantitative phase, the researchers administered the CQ questionnaire among the interpreters. The findings of the quantitative phase showed that there is a significant relationship between the interpreters’ CQ level and the strategies applied to tackle crosscultural problems in interpretation. Interpreters with higher levels of CQ showed a stronger tendency towards elaborative strategies. On the contrary, lower levels of CQ among interpreters resulted in more tendency to apply simple strategies.