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BackgroundFatigue is a common source of distress for cancer survivors. The severity of cancer-related fatigue varies significantly, which may be due to individual differences in host factors.AimThis cross-sectional study aims to explore how demographic, oncological, sociological, psychological, and stress-related hormones levels interact to influence the distinct experiences of fatigue (Cancer-related fatigue [CRF] occurrence and fatigue degree).MethodsA cross-sectional study carried out at the oncology outpatient and ward department of Xiyuan Hospital of China Academy of Chinese Medical Sciences recruited 306 cancer patients between January 2021 to December 2021. General information, fatigue, psychological factors was evaluated by general information questionnaire, the Revised Piper’s Fatigue Scale-Chinese Version (RPFS-CV), and the self-report Hospital Anxiety and Depression Scale (HADS). Stress-related hormones were measured with chemiluminescent enzyme immunoassay (Zhengzhou Antobio).Results306 patients were included, 229 (74.8%) were diagnosed with CRF, including 94 (41.0%) with mild fatigue, 121 (52.8%) with moderate fatigue, and 14 (6.1%) with severe fatigue. Multivariate regression analysis showed that higher depression scores, aldosterone levels may increase the risk of CRF. Patients who are obese (Body mass index ≥ 28 kg/m2) may help to reduce the risk of CRF. Other contributing factors for increased levels of fatigue (p< 0.05) include being female, having anxiety, depression and high aldosterone levels.ConclusionThe research suggested that CRF was a common symptom in cancer survivors and pay attention to these influencing factors may help to better identify patients susceptible to fatigue and provide long-term, targeted interventions.