Objective The aim of this study was to evaluate the clinical value of VEGF、CEA levels for immunotherapy in lung cancer.Methods A total of 100 patients with confirmed NSCLC were enrolled and randomly divided into observation group (immune combined with chemoradiotherapy or immune combined with antivascular therapy, n=50) and the control group (chemoradiotherapy, n=50). The relationship between the level of VEGF, CEA and the short-term efficacy of immunotherapy after two cycles of treatment was investigated in this study. Results The short-term curative effect of the observation group was better than that of the control group, and the objective remission rate was higher (40% vs 22%), but there was no significant difference (P<0.05). Further analysis showed that the efficacy was significantly improved in patients treated with immunotherapy alone (56% vs 22%). A univariate analysis showed that the serum levels of VEGF and CEA at baseline were significantly correlated with the short-term outcome. The dynamic monitoring of serum VEGF and CEA in the two groups before and after treatment showed that the levels of VEGF in the effective patients were significantly lower than those before treatment (P<0.05), however, the CEA level of the patients with immune combined with anti-vascular therapy had no significant change. In addition, multivariate analysis showed the rate of VEGF decline was significantly related with the short-term efficacy (HR=0.085,95%CI 0.009-0.857, P<0.05). 44% patients who received immunotherapy combined with chemoradiotherapy showed benefit with VEGF level decreasing more than 20%, while 80% patients who received immunotherapy combined with antivascular therapy showed benefit. Conclusion The better short-term efficacy is from immunotherapy compared with radiotherapy. Serum VEGF levels is significantly reduced in in lung cancer patients with effective immunotherapy. The decrease rate of VEGF after two cycles of treatment is a potentialpredict marker for the short-term efficacy of immunotherapy, which may be used as a sensitive tool for the development of clinical strategies of this kind of drugs