〔Abstract〕 Objective To predict and analyze the mechanism of downregulation of HNF4α expression in hepatocellular carcinoma(HCC) by bioinformatics analysis. Methods The promoter sequence of HNF4α gene obtained from NCBI GenBank was analyzed by transcription factor prediction software, including PromotorScan, Patch, P-Match and AliBaba2. Meanwhile, the down-regulated genes in human HCC were screened by Liveratlas. Then the intersected genes were analyzed based on the data extracted from TCGA database. Results The promoter of the corresponding transcript of human HNF4α gene in HCC is about 1 471 bp. After removing duplication, the pool of predicting transcription factor binding sites covers 225 transcription factors by using online software. A total of 2 538 down-regulated genes in HCC were extracted from liveratlas online gene database, and 17 transcription factors were obtained by compared with the transcription factor pool predicted above. The correlation analysis indicated that HLF(r=0.553 4), RREB1(r=0.407 9) and RXRA(r=0.424 7) were positively correlated with the expression of HNF4α. Conclusion Bioinformatics analysis indicates that HLF, RREB1 and RXRA may be involved in the transcriptional regulation of HNF4α expression in liver. The faint expression of one or more of them may be related to the down-regulation of HNF4α expression in the development of HCC.