Background: Functional polymorphisms on methylenetetrahydrofolate reductase (MTHFR) gene are reported to be involved in the etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P), but the conclusions are still inconsistent. The aim of our study is to investigate the association between the susceptibility of nonsyndromic cleft lip with or without cleft palate (NSCL/P) and MTHFR C677T polymorphism in Chinese Han population．Methods: A case-control study was performed, followed by a Meta-analysis. Electronic databases including PubMed, Embase, CNKI, VIP and Wanfang database were searched for relevant literature from inception of databases to November 2020. Meta-analysis was performed using Revman 5.3 and STATA 12.0 software. Results: The case-control study included 358 NSCL/P cases and 354 controls, which indicated that the variant T allele significantly increased NSCL/P risk in Southern China. Then, in the present Meta-analysis, a total of nine case-control studies with 1444 cases and 1555 controls were included. Overall, there was a significant association between MTHFR C677T polymorphism and NSCL/P susceptibility under all genetic models. The subgroup analysis of NSCL/P types showed significantly increased risk of CLO but not CPO or CLP. In terms of the stratified analysis by geographical location, a significantly association was observed in Southern China under all genetic models, while there was no significant association in Northern China. Sensitivity analyses, Begg's funnel plot and Egger’s regression test further suggest the stable and trustworthy of these results. Conclusion: MTHFR C677T polymorphism is associated with the risk of NSCL/P in Chinese Han population, especially increasing the risk of NSCL/P in southern Chinese Han populations.