We conducted a comprehensive meta-analysis of 4 case-control studies to explore the association between polymorphisms of Msh homeobox 1 (MSX1) and transforming growth factor-β1 (TGF-β1) genes and hypodontia. A total of 643 tooth agenesis cases and 733 healthy controls were included in this study. The meta-analysis results showed that the T allele and T carrier (CT + TT) of rs1095 in the MSX1 gene were positively associated with hypodontia susceptibility. However, the T allele and T carrier (TC + CC) of rs12532 and rs8670 showed no association with cancer susceptibility. In addition, there were no strong associations between the T allele and T carrier (CT + TT) of C509T and the A allele and A carrier (AG + AA) of G800A in the TGF-β1 gene polymorphisms between patients with tooth agenesis and healthy subjects. In conclusion, these meta-analysis results demonstrated that polymorphisms in the rs1095 region of the MSX1 gene may influence the transcriptional activity of this gene and are associated with hypodontia in humans. However, the association between the TGF-β1 gene and sporadic tooth agenesis is not well understood, and further studies are required to explore the correlation between the TGF-β1 gene and hypodontia.