Objective To explore the influencing factors for cancer-related fatigue in non-small cell lung cancer (NSCLC) patients. Methods Clinical data of 105 NSCLC patients admitted to Fifth Medical Center of Chinese PLA General Hospital from June 2020 to October 2023 were collected and retrospectively analyzed. According to the Piper fatigue scale score, they were divided into non or mild fatigue group (n=43) and moderate to severe fatigue group (n=62). SPSS statistics 26.0 was used for statistical analysis. Data comparison between two groups was performed using t test orχ² test depending on data type. Multivariate logistic regression analysis was applied to identify the influencing factors for the occurrence of cancer-related fatigue in these NSCLC patients. Results Among the 105 NSCLC patients, 20 had no fatigue, 23 had mild, 29 had moderate, and 33 had severe fatigue. The incidence of cancer-related fatigue was 80.95% (85/105) in the cohort. There were significant differences between the non or mild fatigue group and the moderate to severe fatigue group in terms of age, predisease smoking, depression, adverse reactions, white blood cell count, hemoglobin level and platelet count (all P<0.05). Multivariate logistic regression analysis showed that age ≥60 years (OR=3.625,95%CI 1.903-6.585), smoking before illness (OR=3.445,95%CI 1.827-6.832), adverse reactions (OR=2.309,95%CI 1.352-3.943), low white blood cell count (OR=4.689,95%CI 1.825-6.332), high hemoglobin concentration level (OR=2.486,95%CI 1.172-4.485) and high platelet count (OR=2.134,95%CI 1.347-4.032) were all risk factors for cancer-related fatigue in NSCLC patients (all P<0.05). Conclusion The incidence of cancer-related fatigue is relatively high in NSCLC patients, and its occurrence are affected mainly by age, smoking before illness, adverse reactions, low white blood cell count, high hemoglobin concentration level, and high platelet count.