Objective:To analyze the expression level and prognostic value of prefoldins (PFDs) family in hepatocellular carcinoma (HCC) by bioinformatics approach.Methods:GEPIA2 database was employed to obtain the mRNA expression data of PFDs family members in HCC and its correlation with clinical staging. The correlation between the expression levels of PFDs family members and tumor grading was analyzed by UALCAN database. Immunohistochemical images of PFDs family members in HCC and normal liver tissues were obtained and compared by HPA database. The effect of PFDs family members expression on the survival of HCC patients was assessed by Kaplan-Meier plotter database. Clinical data of HCC patients were downloaded from TCGA. PFDs family members and related pathological parameters were subjected to multivariate Cox's regression analysis. Enrichment analysis of PFDs family proteins was carried out by DAVID 6.8 bioinformatics tool. The relationship between the expression levels of PFDs family members and immune infiltration of HCC was analyzed by TIMER 2.0 database.Results:The expression levels of PFDN1, PFDN2, PFDN3 and PFDN4 mRNA and protein in HCC tissues were significantly higher than those in normal liver tissues (P<0.05), which were positively correlated with tumor grading and clinical staging of HCC patients (P<0.05). The survival time of HCC patients with overexpression of PFDN1, PFDN2, PFDN3 and PFDN4 genes was significantly shorter (HR=1.47, 1.45, 1.61, 1.66; P<0.05). PFDN1, PFDN2 and PFDN4 were the independent prognostic factors of HCC patients (HR=1.58, 1.64, 2.04; P<0.05). Gene ontology (GO) and KEGG pathway analyses showed that PFDs family molecules played a role in RNA and mRNA splicing and decomposition, and participated in RNA transport, mRNA monitoring pathway and ribosome synthesis in eukaryotes and other related signaling pathways. The expression of PFDs family members was positively correlated with the expression of helper T cells (Th) 2, CD56+NK cells and plasma cell-like dendritic cells in HCC, whereas negatively associated with the expression of Th17, neutrophils and central memory T cells.Conclusions:High expression of PFDs family members in HCC tissues is correlated with the poor prognosis of HCC patients. The biological function of PFDs is intimately associated with splicer and immune cell infiltration.