Objective: To investigate the clinical efficacy and adverse reactions of anlotinib in the treatment of advanced non-small cell lung cancer(NSCLC). Methods: The clinical data of 45 patients with advanced non-small cell lung cancer who failed in multi-line treatment and poor tolerance to anti-tumor treatment in the affiliated Hospital of Xuzhou Medical University from June 2017 to January 2019 were analyzed retrospectively. The efficacy, progression-free survival(PFS) and adverse reactions of the patients were evaluated comprehensively. Results: A total of 45 patients were enrolled, including 24 cases in a single group and 21 cases in a combination group(17 cases combined with albumin-bound paclitaxel chemotherapy and 4 cases combined with nivolumab immunotherapy). Among the 45 patients, partial remission(PR) accounted for 4.4%(2/45), stable disease(SD) accounted for 88.9%(40/45), progressive disease(PD) accounted for 6.7%. The objective response rate(ORR) was 4.4%, and the disease control rate(DCR) was 93.3%. The median PFS of 45 patients was 3.70 months. The survival rate of patients with different treatment regimens and short-term effects was significantly different from that of patients with short-term efficacy(P<0.05). Th e results of log-rank test showed that there was significant difference in the survival rate of patients with different treatment regimens and short-term effects. Th e PFS in the single drug group was 3.30 months, and the PFS in the combination group was 5.30 months. Th e PFS in the combination group was bett er than that in the single drug group. Th e adverse reactions of 45 patients included hypertension, fatigue, thyroid dysfunction, hand and foot syndrome, and so on. Th e common adverse events of grade 3 included hypertension, myelosuppression and hand and foot syndrome. No adverse events of grade 4 or above were found in this study. Conclusion: Anlotinib has bett er disease control and survival benefits in advanced non-small cell lung cancer patients with failed second-line treatment, and the adverse reactions are relatively small.