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INTRODUCTION: Alcohol-related liver cirrhosis (ALC) is a progressive liver disease that may result from excessive alcohol abuse. Endotoxemia induced by ethanol consumption represents a strong stimulus for Kupffer cells to secrete Tumor necrosis factor-α (TNF-α). TNF-α induces an inflammatory response that often leads to chronic liver injury. It plays a key role in the pathogenesis of alcohol-related liver disease. Our study aimed to estimate the association of ΤNF-α promoter polymorphisms at two positions (-238G˃A and -308G˃A) with ALC susceptibility from one group of ALC patients from Serbia. A total of 118 patients with ALC and 131 sex and age-matched healthy controls were clinically examined and genetically tested. DNA was extracted from peripheral blood lymphocytes, and genotyping was performed using PCR-RFLP for both promoter variants. We determined the TNF-α genotypes of each participant by the presence of the relevant DNA fragments on agarose gel. Groups were compared using the Chi-Square test; binary logistic regression was used to obtain odds ratios. Concerning the -238G>A variant, a significant association between A allele carriers and risk of ALC (OR=2.36, 95% CI=1.15- 4.83; p=0.019) was observed. We found only one patient with an AA genotype, so we compared the combined AA and GA genotypes with GG genotype. No significant differences were found in either genotype or allelic frequencies of the –308 TNF-α gene variant between the patients and controls (allele frequencies 15.7% vs. 13.4%, p=0.463). The -238 TNF-α –A allele was associated with a higher risk of developing ALC in our group of patients with ALC from Serbia. This variant could represent one of the genetic factors that confer a predisposition to develop ALC. [ABSTRACT FROM AUTHOR]