<i>Objective:</i> The hepatitis B virus X protein (HBx) plays critical roles in cell survival via modulation of signaling pathways. In our previous studies, we reported that HBx inhibited the growth of CCL13-HBx-stable cells (Chang-HBx cells) in vitro and tumor formation in vivo in CCL13-HBx-cell-injected nude mice; however, this inhibition mechanism is unclear. <i>Methods:</i> To investigate the role of HBx in Wnt-3/β-catenin signaling pathways, we focused on the key molecules GSK-3β and β-catenin, and analyzed by Western blotting and immunofluorescence staining. <i>Results:</i> Results indicated that following HBx induction, GSK-3β activity was up-regulated, the expression and accumulation of β-catenin in the nucleus were decreased, and cell proliferation was suppressed. Inhibition of GSK-3β activity by pharmacological inhibitors rescued the expression and accumulation of β-catenin in the nucleus and facilitated cell proliferation and growth following HBx induction. The localization of β-catenin, which is involved in cell proliferation, and mediated by GSK-3β activation was also demonstrated. <i>Conclusion:</i> Our findings suggest that HBx negatively regulated proliferation of CCL13-HBx-stable cells via the GSK-3β/β-catenin cascade.