In summary, we found that host variants near IFNL3 and IFNL4 are associated with spontaneous HCV RNA clearance and that individuals who carry the minor allele of polymorphisms near the IFNL3 gene are less likely to show spontaneous HCV clearance and have increased risk for HCC, particularly in those with HCV genotype 1 infection. Here, IFNL3 is linked to infection.