RAD18 is a crucial mismatch repair gene associated with the post-replication repair, and genetic variations in RAD18 gene are closely related to tumorigenesis. We selected 6 RAD18 SNP and performed mismatch amplification PCR on 650 cases of CIN III, 580 cervical squamous cell carcinoma (CSCC), and 1320 healthy controls. The RAD18 rs250403 GG and G allele (AG†+†GG) genotype risk in CIN III and CSCC were significantly increased. The results showed a significant correlation between the GG genotype of rs615967 and the risk of CIN III and CSCC. Carriers of the G allele (AG†+†GG) at RAD18 rs615967 also had an increased risk. More noteworthy was that the RAD18 rs250403 (A/G) and rs615967 (A/G) haplotypes associated with high risk of CIN III and CSCC were AG-GG, GG-AA, GG-AG, and GG-GG. Clinical data analysis further showed that the polymorphisms of RAD18 rs250403 and rs615967 were significantly correlated with prognostic indicators such as family history of tumor, differentiation grade, lymph node metastasis, and vascular involvement. RAD18 protein expression was significantly decreased in CSCCs with the rs615967-AG and rs615967-GG genotype. In summary, the 2 genetic polymorphisms of the RAD18 were associated with susceptibility and prognosis in CIN III and CSCC, and specific high-risk haplotypes of these 2 SNPs could serve as genetic predictive biomarkers.