Abstract: Objective Systematically review the efficacy and safety of Cetuximab for advanced head and neck squamous cell carcinoma (NHSCC). Methods Databases including PubMed, EMBASE, Cochrane Library, OVID, CBM, CNKI, VIP and Wanfang were comprehensively searched. We conducted quality assessment using the method recommended by Cochrane handbook and pooled analysis using RevMan 5.0. Result Six trials with 2 061 patients were included. Compared with controlment, Cetuximab combined therapy decreased risk of disease progression HR=0.72, 95%CI (0.55, 0.94) and death HR=0.8, 95%CI (0.7, 0.92), and improved response rate RR=1.65, 95%CI (1.0, 2.73) and disease control rate RR=1.44, 95%CI (1.06,1.98). Meanwhile, in terms of safety, significant differences were found in aspects of acne-like rash, infusion reaction, hypomagnesemia, sepsis, anorexia, and mucositis. Condusion Regardless of serious and uncontrollable adverse event, Cetuximab could improve OS, PFS, response rate and disease control of HNSCC patients. While clinical trials with large samples and high quality are still warranted to support this conclusion.