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Hepatocellular carcinoma (HCC) is a severe complication of advanced alcoholic liver disease, which is modulated by genetic predisposition. Identifying new genetic loci might improve screening. Genetic variation of <i>SAMM50</i> was linked to HCC. We aimed to validate this finding in a large cohort of patients with advanced alcoholic liver disease (ALD). A large, well-characterised cohort of patients with alcoholic cirrhosis without (<i>n</i> = 674) and with (<i>n</i> = 386) HCC, as well as controls with HCC due to viral hepatitis (<i>n</i> = 134), controls with heavy alcohol abuse without liver disease (<i>n</i> = 266) and healthy subjects (<i>n</i> = 237), were genotyped for <i>SAMM50</i> rs3827385 and rs3761472 and for <i>PNPLA3</i> rs738409. Genotype frequencies were compared between patients with alcohol-associated cirrhosis with and without HCC by uni- and multivariate analysis. Minor variants in both <i>SAMM50</i> rs3827385 and rs3761472 were significantly more frequent in patients with alcoholic HCC versus alcoholic cirrhosis and versus the control cohorts. An even stronger association was noted for <i>PNPLA3</i> rs738409. The univariate analysis resulted in an odds ratio (OR) of 1.8 for carriers of at least one minor variant of <i>SAMM50</i> rs3827385 and rs3761472 (each <i>p</i> < 0.001), but this association was lost in multivariate analysis with age (OR 1.1/year), male sex (OR 3.2), diabetes (OR 1.9) and carriage of <i>PNPLA3</i> 148M (OR 2.1) remaining in the final model. Although minor variants of both <i>SAMM50</i> loci are strongly associated with alcoholic HCC, this association is not independent of carriage of the well-known risk variant <i>PNPLA3</i> 148M.