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Objective To comprehensively evaluate the expression level， prognostic significance and potential transcriptional regulatory mechanisms of MAGEA4 and MAGEC1 in hepatocellular carcinoma （HCC） tissues based on bioinformatic analysis. Methods We collected the HCC-related high-throughput datasets from TCGA and GEO databases， including TCGA-LIHC， GSE10143， GSE20140， GSE87630 and GSE107170. The expression levels of MAGEA4 and MAGEC1 between HCC and adjacent liver tissues were compared. Pearson's correlation analysis was utilized to explore the correlation between MAGEA4 and MAGEC1 expression in HCC tissues. The high- and low-expression of MAGEA4 and MAGEC1 were divided by median. Receiver operating characteristic （ROC） curves were plotted and the area under curve （AUC） was used to assess the discriminatory ability of MAGEA4 and MAGEC1 expression between HCC and adjacent liver tissues. Kaplan-Meier survival analysis was performed to assess the prognostic significance of MAGEA4 and MAGEC1 in HCC patients. Meanwhile， ENCORI and Cistrome DB were used to predict transcription factors （TFs） and miRNAs that regulated the expression of MAGEA4 and MAGEC1. Results Among five included datasetes, the expression level of MAGEA4 and MAGEC1 in HCC tissues was significantly higher than that in adjacent liver tissues （P<0. 05）. The expression of MAGEA4 was positively correlated to MAGEC1 in HCC tissues in TCGA-LIHC, GSE10143 and GSE107170（r = 0. 322, 0. 299 and 0. 482， respectively； all P<0. 01）. MAGEA4 distinguished HCC from adjacent liver tissues with accu⁃ racy from mild to moderate， while MAGEC1 distinguished HCC from adjacent liver tissues with accuracy from mild to favor⁃ able. The up-regulation of MAGEA4 was related to the poor prognosis of HCC patients. Both MAGEA4 and MAGEC1 had the targeted relationships with hsa-miR-1827. The transcription factors with potential regulation with MAGEA4 and MAGEC1 were MYC and TFAP2A. Conclusions MAGEA4 and MAGEC1 are significantly up-regulated in HCC tissues and the up-regulation of MAGEA4 is a risk factor for the prognosis of HCC. Hsa-miR-1827 and transcription factors MYC and TFAP2A， might be the regulatory factors of MAGEA4 and MAGEC1 in common. [ABSTRACT FROM AUTHOR]