The odds of developing HCC in patients with HBV-HCV co-infection were significantly increased by: age over 45 years (2.45 times; 95% CI: 1.38-4.36, p = 0.002), cirrhosis (3.87 times; 95% CI: 2.15-6.96, p < 0.001), infection duration ≥5 years (1.62 times; 95% CI: 1.01-2.59, p = 0.046), AFP >20 ng/mL (3.09 times; 95% CI: 1.74-5.48, p < 0.001), and comorbidities (1.85 times; 95% CI: 1.09-3.15, p = 0.022). This evidence concerns the gene AFP and Cirrhosis.