Increasing evidence suggests that miRNA binding-site polymorphism in the 3'-untranslated region (3'UTR) of a target gene could affect that gene's expression, and can be associated with a variety of complex traits. In this study, we find that miR-18a and cell division cycle 42 (CDC42) mRNA, whose expression was inversely correlated, are differentially expressed in porcine placentas during critical stages of placental development. rs55618224 (T>C), a SNP in the 3'UTR region of CDC42 that is perfectly complementary to the miR-18a seed could influence miR-18a-related regulation of CDC42 gene by altering their binding affinity. In addition, CDC42 mRNA was found to have higher expression level in the homozygous TT placentas as compared to those homozygous CC placentas in pigs. Furthermore, we identified a significant association between rs55618224 and total number born per litter. These results suggest the miR-18a binding-site polymorphism in CDC42 3'UTR may impact litter size by regulation of CDC42 gene in porcine placentas.