Objective: To investigate the effect of erlotinib combined with bevacizumab on immune response and serum tumor markers in Methods: From August 2016 to January 2018, 102 patients with advanced non-small cell lung cancer were randomly selected and randomly divided into experimental group and control group according to random number expression method, 51 cases in each group. Both groups were treated with routine basic chemotherapy, while the control group was treated with erlotinib, while the experimental group was treated with erlotinib combined with bevacizumab. The clinical efficacy, serum tumor markers [cytokeratin fragment antigen 21-1 (CYFRA21-1), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE) and carbohydrate antigen 125 levels] and the occurrence of adverse reactions were observed.Results: The results showed that after treatment, the DCR of the experimental group and the control group were 96.08% and 82.35%, respectively. The experimental group was significantly higher than the control group (P < 0.05). After treatment, the levels of CYFRA21-1, CEA, NSE and CA125 in the two groups were significantly decreased, and the levels of serum tumor markers in the experimental group were significantly lower than those in the control group (P < 0.05). Compared with before treatment, after treatment, the levels of NK, CD4+/CD8+, CD4+, CD3+ in the two groups were significantly increased, and the levels of CD8+ in the experimental group were significantly lower than those in the control group, and the levels of NK, CD4+/CD8+, CD4+, CD3+ in the experimental group were significantly higher than those in the control group, and the levels of CD8+ in the experimental group were significantly lower than those in the control group (P<0.05). The incidence of adverse reactions in the experimental group was 23.53%,Conclusion: Erlotinib combined with bevacizumab in the treatment of advanced non-small cell lung cancer has definite clinical effect. It can significantly reduce the levels of serum tumor markers such as CYFRA21-1, CEA, NSE, and CA125, and improve the immune response of patients with advanced non-small cell lung cancer. It has high safety and wide clinical application value.