Objective To systematically review the efficacy and safety of tyrosine kinase inhibitors combined with chemotherapy versus chemotherapy in advanced non-small cell lung cancer(NSCLC). Methods An electronically search was conducted in The Cochrane Library, PubMed and EMbase databases from inception to December 2016 to collect randomized controlled trials (RCTs) about tyrosine kinase inhibitors combined with chemotherapy versus chemotherapy for NSCLC. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed by using RevMan 5.3 software. Results A total of 12 RCTs involving 6 559 patients were finally included. The results of meta-analysis showed that: The median progression free survival (PFS) (HR=0.86, 95%CI 0.81 to 0.91, P<0.001) and objective response rate (ORR) (HR=1.43, 95%CI 1.20 to 1.70,P<0.001) of tyrosine kinase inhibitors combined with chemotherapy were significantly longer than those of the chemotherapy group. There were no significant differences between two groups in incidence of median overrall survival (OS) (HR=0.91, 95%CI 0.82 to 1.00,P=0.06), fatigue (RR=1.03, 95%CI 0.97 to 1.11, P=0.33), dyspnea (RR=1.01, 95%CI 0.91 to 1.13, P=0.82) and cough (RR=1.01, 95%CI 0.89 to 1.15, P=0.91). However, the incidence of neutrocytopenia (RR=1.16, 95%CI 1.05 to 1.28, P=0.003), thrombocytopenia (RR=1.46, 95%CI 1.23 to 1.73, P<0.001), diarrhea and hypertension (RR=2.91, 95%CI 2.28 to 3.71,P<0.001) of tyrosine kinase inhibitors combined with chemotherapy group were significantly higher than those of the chemotherapy group. The tyrosine kinase inhibitors combined with chemotherapy group had lower rate of anemia (RR=0.86, 95%CI 0.75 to 0.98,P=0.03). Conclusion Compared with chemotherapy alone, tyrosine kinase inhibitors combined with chemotherapy can improve the median PFS and ORR while it can be used as a treatment for advanced non-small cell lung cancer patients. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusion.