To study the association between transforming growth factor alpha gene (TGFalpha) TaqI variant and nonsyndromic cleft lip with or without cleft palate (nsCL/P) in Chinese population, and the interaction with parental smoking.TGFalpha TaqI variant was detected using RFLP-PCR for DNA samples of the 170 triads with nsCL/P affected child. We performed the transmission/disequilibrium test (TDT) and the family-based association study (FBAT) to test the associations between this variant and risk of nsCL/P.It was not found significant distortion of C2 allele at TGFalpha TaqI locus in nsCL/P groups (P > 0.05), however, by stratified analysis, we found that the rate of C2 allele transmission among nuclear families whose fathers were smoking was 1/5 (0.062 - 0.711) as compared with that among nuclear families whose fathers were not smoking, and the OR of interaction between TGFalpha variant and parental smoking is 0.102 (0.017 - 0.619).The parental smoking may interact with TGFalpha variants of Chinese populations in occurrence of nsCL/P, but it remains to have more investigations.