ObjectiveTo systematically review the correlation between the T538C polymorphism in bone morphogenetic protein 4 (BMP-4) and the risk of non-syndromic cleft lip with or without cleft palate (NSCL/P). MethodsWe electronically searched databases including PubMed, The Cochrane Library, EMbase, CBM, CNKI, VIP, and WanFang Data from inception to November 2014, to collect case-control studies of the correlation between the T538C polymorphism in BMP-4 and the risk of NSCL/P. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.2 software. ResultsA total of 6 case-control studies involving 926 cases and 1 110 controls were included. The results of meta-analysis showed that:there was no significant association between the T538C polymorphism in BMP-4 gene and the risk of NSCL/P (C vs. T:OR=1.14, 95% CI 0.78 to 1.66; CC vs. TT:OR=0.75, 95% CI 0.50 to 1.11; CC vs. TT:OR=1.53, 95% CI 0.69 to 3.37; CC vs. CT+TT:OR=1.80, 95% CI 0.96 to 3.38; CC+CT vs. TT:OR=0.90, 95% CI 0.57 to 1.43). Subgroup analysis based on ethnicity showed that, the T538C polymorphism in BMP-4 gene was associated with increased risk of NSCL/P in Asian population (C vs. T:OR=1.54, 95% CI 1.26 to 1.87; CC vs. TT:OR=2.91, 95% CI 1.88 to 4.52; CC vs. CT+TT:OR=2.99, 95% CI 1.99 to 4.49), but decreased risk of NSCL/P in Latin populations (C vs. T:OR=0.69, 95% CI 0.50 to 0.96; CT vs. TT:OR=0.52, 95% CI 0.40 to 0.68; CC+CT vs. TT:OR=0.52, 95% CI 0.35 to 0.78). ConclusionAvailable evidence suggests that the T538C polymorphism in BMP-4 gene may be associated with increased risk of NSCL/P in Asians and decreased risk of NSCL/P in Latinas. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.