The prevalence of cleft lip and palate in human is 1 in 500 live births worldwide. Non-syndromic clefts are a complex trait with both genetic and environmental etiology. Transforming Growth Factor Alpha (TGFα) is a modifier gene which is susceptible to environmental factors, leading to development of sporadic non-syndromic clefts. Objective: To determine the association between maternal exposure to second-hand smoke during pregnancy and TGFα gene polymorphism in cleft children genotype. Methods: Retrospective cohort study was carried out among cleft children with and without maternal exposure to cigarette smoke during pregnancy. The cleft children were selected from the Combined Cleft Clinic at Kota Bharu Dental Clinic. A total of 33 subjects were identified for exposed (16 Males:17 Females) and 32 were identified as non-exposed (20 Males:12 Females) with age range from 3 months to 10 years. The subjects' mothers (age range from 17 to 50 years old) were interviewed using the standard craniofacial deformity registration form. Blood samples were taken from the subjects. DNA was extracted and amplified with PCR. Then RFLP technique was used with enzyme Hinf1 and Nco1 for K region; and Taq enzyme for Taq-1 region. Results: Chi-square (χ2) test detected a significant difference of allele 4 at K region between exposed and non-exposed subjects (95% CI: 1.07, 8.06); p=0.037 but not at Taq-1 region. Simple Logistic Regression analysis revealed that maternal exposure to second-hand smoke for more than 30 minutes per day had the relative risk of 3.82 times of having allele 4 polymorphism among exposed compared to non-exposed subjects (95% CI: 1.29, 11.28) p=0.015. Conclusion: Maternal exposure to second-hand smoke during pregnancy was significantly associated with polymorphism of allele 4 at K-primer region of TGFα gene in sporadic non-syndromic oral cleft patients.