AIM: To investigate genes around the locus D4S2964 affected by loss of heterozygosity (LOH) and their clinical implications.METHODS: Four hundred and forty single nucleotide polymorphisms (SNPs) located at 49 genes around D4S2964 were selected from the National Center for Biotechnology Information website for the SNPs microarray fabrication. LOH of SNPs markers in 112 cases of hepatocellular carcinoma (HCC) tissues and paired adjacent liver tissues were investigated by the SNPs microarray. The correlation between allelic losses with clinicopathological features and overall survival was analyzed.RESULTS: A fine map of LOH of SNPs in genes around D4S2964 was plotted. The average frequency of LOH in genes was 0.39. A correlation between cirrhosis and the FAL index (fractional allelic loss) was found ( P = 0.0202).Larger tumor size was found to be significantly associated with LOH in genes ADP-ribosyltransferase 3 (ART3),nucleoporin 54 kDa (NUP54), scavenger receptor class B, member 2 (SCARB2) and coiled-coil domain containing 158 (CCDC158) ( P = 0.043, P = 0.019, P = 0.001,P = 0.037, respectively). Kaplan-Meier analysis showed that patients with LOH in ARD1 homolog B (ARD1B) and septin 11 (SEPT11) had a significantly lower survival rate than those with retention ( P = 0.021 and P = 0.004,respectively). A Cox regression model suggested that LOH in ARD1B and SEPT11, respectively, were predictors of the overall survival in HCC ( P = 0.006 and P =0.026, respectively).CONCLUSION: LOH in genes around D4S2964 may play an important role in HCC development and progression.LOH in ARD1B and SEPT11 could serve as novel prognostic predictors in HCC patients.