Objective: The ExPRO (External factors influencing patient reported outcomes of patients with malignant diseases) study explored associations between QoL data and environmental factors on the day of questionnaire completion: mean temperature, sunshine hours, season, and lunar phase. Methods: We undertook a cross-sectional analysis of baseline data in the prospective cohort study at two cancer centers in eastern Germany. From December 2020 to December 2021, cancer patients completed the EORTC QLQ-C30 questionnaire upon admission. Statistical analysis was performed to explore associations between QoL data and environmental factors, including temperature, sunshine hours, season, and lunar phases. Results: We received 5040 responses (54% male). QoL scores were highest at 25-30 °C and lowest at 5-10 °C (mean 61.3 vs. 52.6, p <0.001). Insomnia was highest at ≤0 °C and lowest at 25-30 °C (mean 39.3 vs. 29.5, p <0.001). QoL was highest with 8 hours of sunshine and lowest with 0 hours (mean 56.9 vs. 50.9, p = 0.003). Conclusion: Higher temperatures, more sunshine, and summer seasons are associated with higher QoL in cancer patients, while lower temperatures and reduced sunlight are associated with poorer QoL. These findings highlight the need to consider environmental factors in PRO assessments.