Abstract: Objective: To analysis the clinical efficacy and safety of crizotinib combined with pemetrexed for treatment of advanced ALK positive non-small cell lung cancer. Methods: 62 patients with advanced ALK positive non-small cell lung cancer diagnosed (were divided into the control group (33 cases) and the observation group (29 cases) randomly. The control group was crizotinib alone, the observation group was received crizotinib combined with pemetrexed. Compare of the efficacy, survival and adverse reactions between two groups. Results: The total efficiency of the control group and the observation group was 63.6% and 82.6% respectively, the observation group was significantly better than the control group(P﹤0.05); The median PFS was 7.7 and 10.4 months respectively, the observation group was significantly better than the control groups (P﹤0.05); and there was no significantly difference in adverse reactions between the two groups (P﹥0.05). Conclusion: Crizotinib and pemetrexed are effective method of treatment of advanced ALK positive non-small cell lung cancer, combination therapy is better, is an effective and safe treatment