Objective To evaluate the efficacy and side effect of non-conventional fractionated radiotherapy for head and neck cancer.Methods Trials were identified by searching CENTRAL, MEDLINE, EMBASE, Chinese Biological Medicine Database (CBMdisc) and Chinese VIP Database. We handresearched the data from 10 kinds of important Chinese journals. Two reviewers assessed and extracted the studies. The following primary outcomes were assessed: complete relief (CR), overall survival (OS), acute side effect and late side effect. Results Twenty-three trials involving 8 411 patients were included. Thirteen trials were of good quality, and the rest were of poor quality. Meta-analysis of these trials showed that: (1) non-conventional fractionated radiotherapy vs conventional fractionated radiotherapy: ① Only S-HART and CAIR resulted in higher CR, RR=1.21 (95%CI 1.02 to 1.44), 3.31 (95%CI 1.16 to 9.42), respectively; ② Only HRT could improve 2-year OS (RR=1.32, 95%CI 1.13 to 1.54), but this difference wasn’t found in 5-year follow up; ③ Most of the non-conventional fractionated radiotherapy could increase acute side effects, but not the late ones; (2) non-conventional fractionated radiotherapy combined with concurrent chemotherapy vs non-conventional fractionated radiotherapy: ① Only C-HRT resulted in higher CR (RR=1.58, 95%CI 1.18 to 2.11); ② Higher 2-year OS could be gained when combined with chemotherapy (RR=1.35, 95%CI 1.18 to 1.54), and only C-HRT resulted in higher 5-year OS (RR=1.57, 95%CI 1.19 to 2.07). ③ Acute and late side effects of radiotherapy would not increase when combined with chemotherapy. Conclusion It can not be concluded that non-conventional fractionated radiotherapy can improve the CR and OS of head and neck cancer, for a small number of patients, but it will get effect when combined with concurrent chemotherapy, and would not increase acute or late side effects. The effects of HRT and C-HRT should be cared specially.