The aim of the present study was to investigate the effect of low concentration of Cr(VI) on proliferation and self-renewal of hepatic stem/progenitor cells (HSPCs) and their possible mechanism of action. WB-F344 cells, a rat-derived multipotent HSPCs line, were cultured with various doses of Cr(VI) for 24 hours or 30 days. The results showed that low concentration of Cr(VI) inhibited proliferation and self-renewal of WB-F344 cells, in which cell colony formation efficiency and colony diameter were significantly decreased in a concentration dependent manner. Microarray and qPCR results revealed that the expression of several genes belonging to Wnt signaling were downregulated. Consistent with gene expression analysis, treatment of WB-F344 cells with Cr(VI) resulted in reduction of transcriptional activator b-catenin, together with its translocation from nucleus into cytoplasm. Our finding suggested that low concentration Cr(VI) inhibited proliferation and self-renewal activity of WB-F344 cells by suppressing Wnt signaling activity.