In the present study, we simultaneously analyzed the distribution of polymorphic variants in the PD-1, IFNL3, and TLR2 immune-related genes among Italian patients affected by HCV-related CHC, cirrhosis and HCC (n = 450) and we compared the genotype and allele frequencies with those obtained in patients affected by HCV-related lymphoproliferative diseases, such as MC and NHL, (n = 238) and in healthy BD (n = 94). This evidence concerns the gene IFNL3 and hepatocellular carcinoma.