Introduction: Although Muslims constitute nearly one fourth of the global population, many non-Muslims are not familiar with Islam. To address this unique need from such a specific cultural context, the present study aimed to examine the spiritual needs and influencing factors of Indonesian Muslims with cancer. Method: A cross-sectional research design with 122 cancer patients was conducted by using the Bahasa-version Spiritual Needs Questionnaire. Results: The degree of spiritual needs was generally high. Religious needs were the strongest aspect, and “praying five times a day” was the highest scoring item. Gender (p = .04), age (p = .01), and duration of being diagnosed with cancer (p = .01) were associated with spiritual needs. Female gender (p = .005) and older age (p < .001) were predictors of spiritual needs. Discussion: As expected to provide cultural-congruent spiritual interventions, nurses could meet Muslim patients’ need to pray five times a day during hospitalization, thus help them manage and endure the illness.