Objective: Case-control study on mothers of cheilopalatognathus children was conducted, to investigate the maternal physiological and psychological factors for occurrence of cheilopalatognathus. Materials and Methods: One hundred ten mothers of cheilopalatognathus children who were scheduled for one-stage surgery were selected as a research group, and 110 mothers of normal children served as a normal control group at the same time. Trait Anxiety Inventory (T-AI), Life Events Scale (LES), Trait Coping Style Questionnaire (TCSQ), Type C Behavior Scale (CBS), adult Eysenck Personality Questionnaire (EPQ), and homemade general questionnaire survey were employed for the investigation. Results: Compared with the control group, the scores for negative event tension value, anxiety, and depressive factors were higher in the study group (p < 0.05); while the scores for positive event tension value, intellect, optimism, and social support factors were lower (p < 0.05). Regression analysis found that physiological factors included were five: education, changes in body weight during pregnancy, the intake amount of milk and beans, and intake of healthcare products, and supplementary folic acid taken or not, while the psychological factors included were four: positive event stimulation, negative event stimulation, the amount of social support, as well as introvert and extrovert personalities. Conclusion: The study results suggest that pregnant women's physiological and psychological factors can cause changes in cheilopalatognathus incidence, which is expected to be guidance for healthcare during pregnancy, to prevent the occurrence of cheilopalatognathus.