Purpose: This study explored the relationship of spirituality and religiosity as it affects the physical and mental quality of life (pQOL, mQOL) of cancer survivors., Methods: This is a prospective observational study that included adults ≥ 19 years who received treatment for various types of cancer. Patients' QOL was obtained at baseline, 6, and 12 months. Cohorts were categorized according to spirituality/religiosity levels: low spirituality-low religiosity (LSLR), low spirituality-high religiosity (LSHR), high spirituality-low religiosity (HSLR), and high spirituality-high religiosity (HSHR)., Results: Of the 551 eligible, 248 (45%) had HSHR, 196 (36%) had LSHR, 75 (14%) had LSLR, and 32 (6%) had HSLR. The pQOL of LSLR were significantly lower than those with HSHR (p = 0.02). The differences in pQOL between LS and HS were observed among those who have HR (p < 0.0001). Among patients with LR, pQOL did not differ. The mQOL of patients with LSLR was significantly lower than those with HSHR (p < 0.0001). The mQOL of those with HS was significantly higher than those with LS in both cohorts having LR (p < 0.0001) or HR (p < 0.0001). pQOL decreased while mQOL increased over time regardless of spirituality or religiosity levels., Conclusion: Spirituality is important in the improvement of both pQOL and mQOL of cancer survivors, while religiosity may have some impact on pQOL. Clinicians' incorporation of spirituality into cancer treatment facilitates well-rounded care, which offers measurable improvements for patients with an illness, of which the treatment is often arduous, and uncertain., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)