The aim of the present study was to investigate the effects of combined general-epidural anesthesia (CGEA) and total intravenous anesthesia (TIVA) on cellular immunity and prognosis in patients with non-small cell lung cancer (NSCLC) in a Chinese population. One-hundred and twenty NSCLC patients were randomly divided into a TIVA group (n=60) and a CGEA group (n=60) using a random number table. All patients underwent video-assisted thoracoscopic surgery for radical resection. Blood pressure (BP) and peripheral oxygen saturation (SpO2) were measured. Post-operative analgesic effects were evaluated with a visual analog scale pain score. Flow cytometry was applied to measure T lymphocyte subsets [cluster of differentiation (CD)3+, CD4+, CD8+ and CD4+/CD8+] and natural killer cell CD56+. A 3-year follow-up was conducted to observe the prognosis. The analgesic effects of CGEA were identified to be better than those of TIVA. Compared with the TIVA group, the CGEA group demonstrated a shorter time of spontaneous breathing recovery, eyes opening, and extubation, lower heart rate, blood pressure and mean arterial pressure, and higher SpO2. At 24 and 48 h after surgery, CD3+, CD4+, CD4+/CD8+ and CD56+ in the CGEA group were higher than those in the TIVA group. At 72 h after surgery, CD3+, CD4+, CD4+/CD8+ in the CGEA group were higher than those in the TIVA group. These results indicate that CGEA and TIVA effected cellular immunity, and CGEA had a reduced effect on cellular immunity and improved postoperative analgesic effects.