Abstract: OBJECTIVE To investigate the effect of gefitinib combined with thalidomide on the short-term efficacy, quality of life and serum tumor markers in patients with non-small cell lung cancer. METHODS Ninety-eight patients with advanced non-small cell lung cancer who were treated in the Fourth People's Hospital of Zibo City from March 2015 to March 2017 were collected and randomly divided into the observation group(49 cases) and the control group(49 cases). Two groups of patients were treated with DP chemotherapy program. The control group was treated with thalidomide, and the observation group was treated with gefitinib on the basis of the control group. The two groups were treated with 28 d for one cycle, 4 consecutive cycles. The short-term efficacy, improvement of quality of life, improvement of serum tumor markers and adverse reactions were compared between the two groups. RESULTS The total effective rate in the observation group(75.51%) was higher than that in the control group(55.10%)(P<0.05). The improvement rate of quality of life in observation group(79.59%) was higher than that in control group(59.18%)(P<0.05). Serum CA125, CEA and CYFRA21-1 levels decreased in two groups after treatment(P<0.05); the serum CA125, CEA and CYFRA21-1 levels after treatment in the observation group were lower than that in the control group(P<0.05). There was no significant difference in the incidence of leukopenia, thrombocytopenia, nausea, vomiting, fatigue, liver function damage and diarrhea between the two groups. CONCLUSION Gefitinib combined with thalidomide in the treatment of patients with non-small cell lung cancer have significant curative effect, can improve the survival of patients after treatment, can reduce the level of serum CA125, CEA and CYFRA21-1.