Cirrhosis is the fourteenth leading cause of death globally and significantly increases the risk of hepatocellular carcinoma (HCC). Polymorphisms in the vitamin D receptor (VDR) can influence inflammation, fibrosis progression and cancer susceptibility. We analysed the association of genetic polymorphisms of the VDR (VDR-rs2228570, VDR-rs731236 and VDR-rs7975232) in cirrhosis with or without HCC, considering clinical, biochemical profiles and survival. A total of 158 patients with cirrhosis, with or without HCC, were studied and distributed into Group 1 (G1 = 60): cirrhosis and HCC; Group 2 (G2 = 98): isolated cirrhosis and control group (G3 = 225): without liver disease. Genetic polymorphisms were analysed by real-time polymerase chain reaction; clinical and biochemical profiles were obtained from medical records. A significance level of α = 5% was adopted. The homozygous mutant for VDR-rs731236 and rs7975232 predominated in G1 compared to other groups (p < 0.05). For VDR-rs2228570, the homozygous mutant predominated in patients, while heterozygotes were found in controls (p > 0.05). A positive correlation between vitamin D and parathyroid hormone was observed in patients (R² = 0.3273). VDR-rs2228570 emerged as a protective factor for G2 (p = 0.0057) and was associated with increased survival, as was rs7975232. In conclusion, VDR-rs731236 and VDR-rs7975232 are associated with cirrhosis and HCC, with VDR-rs7975232 identified as independent predictors for isolated cirrhosis. VDR-rs2228570 confers protection and is associated with increased survival in cirrhosis, as well as a better clinical profile for both conditions in the Brazilian cohort. These findings highlight the potential clinical relevance of VDR polymorphisms as biomarkers for risk assessment and prognosis in cirrhosis and HCC.