Objective To evaluate the effectiveness and safety of Endostar combined with chemotherapy for non-small cell lung cancer (NSCLC). Methods Randomized controlled trials (RCTs) on Endostar combined with chemotherapy for NSCLC were searched in The Cochrane Library, MEDLINE, EMbase, VIP, CNKI, CBMdisc and other electronic databases. The quality of RCTs meeting inclusion criteria was evaluated and the data were extracted; meta-analyses were performed with RevMan 5.1 software, and then the GRADE System was used to rate the level of evidence and strength of recommendation. Results Among the 18 RCTs involving 1 825 cases included, 1 816 cases met the inclusion criteria. Meta-analyses showed that: compared with the single chemotherapy, Endostar combined with chemotherapy could increase the total effective rate (RR=1.85, 95%CI 1.56 to 2.11, Plt;0.000 01), and the clinical benefit response (RR=1.21, 95%CI 1.14 to 1.29, Plt;0.000 01), but decrease the incidence risk of leukopenia (RR=0.89, 95%CI 0.82 to 0.97, P=0.006). There were no signficant differences between the two groups in decreasing thrombocytopenia (RR=0.87, 95%CI 0.74 to 1.03, P=0.10), impaired renal function (RR=0.96, 95%CI 0.69 to 1.34, P=0.82), nausea and vomiting (RR=0.92, 95%CI 0.84 to 1.01, P=0.08) and other side effects. Based on GRADE, the level of evidence was Grade C, and the strength of recommendation was 2. Conclusion The present results of clinical trials show that Endostar combined with chemotherapy for NSCLC is a safe and effective therapy without increasing the toxic reaction and side effects; and based on GRADE, the level of evidence was Grade 2C, and the strength of recommendation was 2. However, in view of the limitations of this study, it is suggested that large-scale, high-quality researches on basic and clinical fields should be performed to further verify the above conclusion by critical outcome indicators.