We aim to investigate the relationship between self-efficacy, cancer-related fatigue, and quality of life in patients with resected lung cancer. A prospective cohort among 452 patients with resected NSCLC was conducted in 2014 to 2015. The self-efficacy, cancer-related fatigue, and quality of life assessments were investigated in the 3-month follow-up by General Self-Efficacy Scale (GSES), Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), and Short Form Health Survey (SF-36), respectively. Structural equation modelling was used to evaluate the relationships between the latent variables. Structural equation modelling analysis showed that both GSES (beta = 0.69, p < 0.05) and MFSI-SF (beta = -0.46, p < 0.01) had direct effect on SF-36; GSES also can indirect effect on SF-36 though MFSI-SF (beta = -0.42, p < 0.01). The model fit indices demonstrated a reasonable fit (chi(2) = 27.221, CFI = 0.911, GFI = 0.962, RMSEA = 0.051). The results showed self-efficacy has direct and indirect effect on quality of life in patients with resected lung cancer. Furthermore, cancer-related fatigue, as mediated variables, can mediate the relationship between self-efficacy and quality of life. In the future, self-efficacy interventions are need for improving quality of life in patients with resected lung cancer.