Abstract: Objective To evaluate the association of MTHFR C677T polymorphism with the clinical outcomes and toxicities of 5-FU-based chemotherapy in advanced colorectal cancer and guide the clinical individualized treatment. Methods The PubMed database, EMBASE, Chinese National Knowledge Infrastructure, Cochrane Library were searched（up to March 27, 2017）, screening cohort studies or case control studies about the association of MTHFR C677T polymorphism with the clinical outcomes and toxicities of 5-FU-based chemotherapy in advanced colorectal cancer according to inclusive and exclusive criteria, collecting the data and assessing the quality of researches, then meta-analysis was carried about by RevMan5.3. Results A total of 19 studies were included in the meta-analysis. The result showed no association between MTHFR C677T polymorphism and the clinical outcomes of Fluorouracil-based chemotherapy in advanced CRC patients. The pooled OR values for 677CT+677TT compared with 677CC was 1.06（95%CI 0.71~1.58,P=0.77）. In the subgroup analysis by 5-FU mono therapy and combination therapy, no statistically differences were found. The pooled HR for death in patients with CT+TT was 1.05（95%CI 0.93~1.18,P=0.42）. There is also no significant difference between MTHFR C677T polymorphism and grade 3~4 toxicity of chemotherapies, the OR values for CT+TT compared with CC was 0.88（95%CI 0.74~1.05,P=0.16）. Conclusion The results of meta-analysis suggests there was no association of MTHFR C677T polymorphism with the clinical outcomes and toxicities of Fluorouracil-based chemotherapy in advanced CRC patients. Further studies are needed to validate the conclusion.