ObjectiveWe aimed to study the association between rs7525173, rs2236518, rs2493264 single nucleotide poly-morphism (SNP) in the PRDM16 gene, smoking, alcohol exposures, and nonsyndromic cleft lip with or without cleft palate (NSCL/P).MethodsA total of 157 case-parent trios were selected, and SNPs were genotyped by using ligase detection reaction (LDR) and direct sequencing methods. Transmission disequilibrium test (TDT) and linkage disequilibrium (LD) tests were con-ducted to analyze the data. A total of 1 710 patients with orofacial clefts and 956 healthy newborns were enrolled in the epide-miological survey. The smoking and drinking exposures of parents during early pregnancy were analyzed.ResultsThe C allele at rs2236518 was over-transmitted for NSCPO (PPConclusionThe rs2236518 at PRDM16 gene, maternal smoking, maternal passive smoking, and maternal drinking were closely related to the occurrence of NSCL/P.