〔Abstract〕 To investigate the regulatory mechanism of nucleotide excision repair (NER) in hepatocel- lular carcinoma (HCC) . Methods Based on the expression levels of genes in the NER pathway , we performed molecular typing of HCC using the TCGA database . HCC cell lines were constructed through the knockdown of RNA binding motif protein 39 (RBM39) using siRNA . HCC cell lines were constructed through the overexpression of RBM39 using RBM39 plasmid . Cells were treated with Indisulam , a reagent that induces RBM39 protein degra- dation . Western blot and real-time fluorescence quantitative PCR were used to detect the expression levels and changes of mRNA and protein of RBM39 and excision repair cross complementation group 1 (ERCC1) ; flow cytom- etry was used to detect NER efficiency; CCK-8 assay was used to detect cell viability . Results HCC patients were categorized into three types—C1 , C2 , and C3—based on NER activity , with the C3 subtype showing the highest NER activity (P < 0. 0001) . In the groups transfected with RBM39 siRNA or treated with Indisulam , the NER re- pair efficiency decreased compared to the control group (P < 0. 01) , the cell survival rate decreased (P < 0. 01) , and both the mRNA and protein expression of ERCC1 were reduced (P < 0. 01) . In contrast , in the RBM39 over- expression group , the mRNA and protein expression of ERCC1 were enhanced compared to the control group (P < 0. 01) . Conclusion RBM39 may influence NER repair efficiency by regulating ERCC1 expression in HCC .