Background: Quality of life is a multidimensional concept that involves physical, social, emotional, and functional well-being. Spirituality represents a potentially influential factor in the quality of life. This study aimed to evaluate the quality of life and spirituality among cancer patients. Methods: A cross-sectional study was carried out on 354 cancer patients in Palestine. A self-administered questionnaire was used for data collection. The questionnaire was made up of 4 sections: sociodemographic factors, clinical data, FACT-G, and FACIT-sp. Results: A total of 354 cancer patients with a mean age of 46.4 ± 15.3 years were enrolled in the study. The spiritual well-being of patients reported in this study was measured by using the median FACIT-Sp total score, and it was 35 (IQR: 29-42). The quality of life of patients was measured using the median of the FACT-G total score, and it was 63 (IQR: 52-85). The FACT-G score was significantly variable based on several factors including age, marital status, cancer type, presence of metastasis, presence of treatment side effects, and the period since diagnosis ( P-value < .05). The FACIT-Sp total score had a significantly strong positive relationship with FACT-G total score ( r = .705, P < .001). Moreover, moderate to strong significant correlations were found between spirituality and quality of life subscales. Conclusions: Quality of life among cancer patients is affected by their basic and clinical characteristics and is highly correlated with their spirituality level. Thus, addressing palliative support through spiritual care besides primary clinical treatment is of great importance to improve the quality of life among cancer patients.