Abstract: Objective To explore the risk factors of perinatal congenital heart disease (CHD) in Western Hainan, and provide preventive measures. Methods Perinatal births data from fifteen medical institutions in Western Hainan from 2012 to 2017 were collected. Totally 1 382 CHD cases were included in our study, with a 1∶1 matched normal control cohort. The baseline data of the two groups were collected. Univariate analysis and multivariate logistic stepwise regression analysis were used to analyze the risk factors of CHD. Results Univariate analysis showed that father's education level, mother's education level, abnormal birth history, CHD family history, smoking during pregnancy, alcohol drinking during pregnancy, perm or hair dye, early pregnancy infection, medication during early pregnancy, or radiation exposure, house decoration, work environment pollution and mother syphilis infection during pregnancy were associated with the occurrence of CHD (all P＜ 0.05). Multivariate logistic stepwise regression analysis showed that abnormal birth history (OR, 2.614; 95% CI, 1.718-3.926), alcohol drinking during pregnancy (OR, 4.182; 95%CI, 2.956-5.862), smoking during pregnancy (OR, 4.526; 95% CI, 3.215-6.913), early pregnancy infection (OR, 2.317; 95% CI, 1.502-3.473), medication during early pregnancy (OR, 5.112; 95% CI, 3.426-8.104), radiation exposure history during pregnancy(OR, 9.204; 95% CI, 5.802-20.624), house decoration (OR, 7.318; 95% CI, 4.517-12.438), working environment pollution (OR, 2.873; 95% CI, 1.768-4.305) and mother syphilis infection (OR, 8.916; 95% CI, 5.308-16.127) were independent risk factors for the occurrence of CHD. Conclusion There are many risk factors for perinatal CHD in Western Hainan. We should strengthen health education for pregnancy so as to reduce the incidence of CHD.