Infection with hepatitis C virus (HCV) is a major risk factor for hepatocellular carcinoma (HCC) in India. The study was designed to investigate the clinical and molecular profiles of HCV related HCC cases in Indian patients. In a prospective study, 68 HCV related HCC, 55 HCV related chronic hepatitis, and 68 HCV related patients with cirrhosis were included. Glutathione S-transferase gene polymorphism was analyzed in all the cases. The sex ratios were 5.18:1, 1.39:1, and 0.83:1 with mean age of 50.57 ± 12.47, 39.41 ± 13.34, and 46.08 ± 15.06 years, respectively, in three groups. Amongst the HCV related HCC cases seen in India, 49.2% (30 out of 68) were with Okuda stage I while 34.4% (21 out of 68) cases were classified as stage II. Older age, poor standards of living, HCV genotype 4, smoking, and null genotypes of GST were the risk factors associated significantly with the development of HCC. In 55.9% cases (38 out of 68) the size of the tumor was ≥5 cm while in 38.2% cases (26 out of 68) the size was between 2 and 5 cm, indicating an advanced stage of the disease at presentation.