Abstract: Objective To observe the clinical efficacy and safety of anlotinib combined with docetaxel as the second-line therapy for patients with advanced non-small cell lung cancer(NSCLC) without driver gene mutation, and to provide theoretical basis and therapeutic strategy. Methods Thirty-six patients were selected from May 2018 to May 2019 in the First Affiliated Hospital of Bengbu Medical College. These patients were treated with anlotinib combined with docetaxel in second-line therapy of advanced NSCLC without driver gene mutation who had failed in first-line therapy. The clinical efficacy, safety and adverse reactions were evaluated. Results The median progression-free survival of anlotinib combined with docetaxel was 4.5 months(ranging from 1.5 months to 15.4 months). After treatment, the number of CR, PR, SD and PD was 0, 6, 25, 5 respectively, and DCR and ORR were 86.11% and 16.67% respectively. In 31 patients with controlled diseases, 20 patients made progress again during the observation period. Cox multivariate analysis showed that staging was an independent risk factor for prognosis(P=0.032). Common adverse reactions included hypertension, fatigue, abnormal liver function, hand-foot syndrome, etc. Conclusion The efficacy of anlotinib combined with docetaxel as second-line therapy for patients with advanced NSCLC without driver gene mutation is positive, and the incidence of adverse reactions are tolerable. This therapy can be used as second-line treatment option for advanced NSCLC patients without gene mutation.