In univariate and multivariate analyses, a training cohort of HCC patients homozygous for endothelial nitric oxide synthase (eNOS) haplotype (HT1:T-4b at eNOS-786/eNOS VNTR) had a worse mPFS (2.6 months vs. 5.8 months, HR = 5.43, 95% CI: 2.46–11.98, p < 0.0001) and OS (3.2 months vs. 14.6 months, HR = 2.35, 95% CI: 1.12–4.91, p = 0.024) when compared with other haplotypes. This evidence concerns the gene NOS3 and hepatocellular carcinoma.