The aim of the study was to investigate the association between environmental factors and nonsyndromic cleft of the lip and/or palate (NSCL/P) in Yantai District, China. A retrospective case-control study was carried out. A total of 236 NSCL/P children were selected from Department of Oral and Maxillofacial Surgery of Yantai Stomatological Hospital between September 2013 and December 2016 as cases; 209 controls were chosen from other diagnosis in the same department during the same period. The 2 groups matched age and sex. The parents of participants were inquired regarding the risk factors, and the answers were filled in a questionnaire by physicians. Chi-square and multivariate logistic regression analysis were used to analysis the data. There was significantly increased NSCL/P risk with high maternal age (P =0.002), family history (P = 0.001), abortion history (P = 0.033), poor parental education level (P = 0.008), maternal smoking (P = 0.044), maternal alcohol (P = 0.039), common cold or fever (P = 0.035), drug use (P = 0.006), and maternal stress (P = 0.049). Reduced NSCL/P risk was found with folic acid supplementation (P = 0.005), adequate maternal age (P = 0.002), and high parental education (P = 0.001). The proper amount of folic acid, the appropriate age of childbearing, and the high education were the protective factors of NSCL/P, whereas family history, abortion history, drug use during pregnancy, maternal tobacco and alcohol, and maternal stress were the risk factors for NSCL/P in Yantai District, China.