〔Abstract〕 Objective To explore the possible mechanism of glycyrrhetinic acid on inhibiting malignant biological behaviors of melanoma by Wnt/β-catenin pathways. Methods The melanoma cells B16-F10 were selected as the research objects. The concentration gradient tests(0, 1, 2, 4 μmol/L) were conducted by MTT. The cells given cisplatin intervention was enrolled as positive controls. The cells invasion and migration were detected by Transwell chamber assay. The expression levels of Wnt/β-catenin pathway proteins, invasion and migration related proteins(MMP-2, MMP-9) in B16-F10 cells were detected by Wester blot. The xenograft models of nude mice were constructed, and they were divided into control group(without drugs treatment) and glycyrrhetinic acid group(40 mg/kg). The growth of tumor tissues, and expression levels of Wnt/β-catenin pathway proteins, invasion and migration related proteins were observed. Results MTT results showed that glycyrrhetic acid could inhibit the proliferation of B16-F10 cells in a concentration-dependent manner. The inhibition effect of glycyrrhetic acid(≥2 μmol/L) was significant on the proliferation of B16-F10 cells(P<0.05). The results of Transwell chamber assay showed that compared with control group, invasion and migration abilities of B16-F10 cells were significantly reduced after treatment with glycyrrhetinic acid(2, 4 μmol/L)(P<0.05). Wester blot results showed that compared with those without glycyrrhetinic acid treatment, expression levels of MMP-9, MMP-2, Wnt1 and β-catenin protein in B16-F10 cells significantly decreased after treatment with glycyrrhetinic acid(2, 4 μmol/L)(P<0.05). The results of tumor-bearing assay showed that compared with control group, weight and volume of tumors significantly decreased in glycyrrhetinic acid group, and expression levels of Wnt1, β-catenin, MMP-9 and MMP-2 proteins also significantly decreased(P<0.05). Conclusion Glycyrrhetinic acid can significantly inhibit the malignant biological behaviors of melanomain vitroandvivo. And its mechanism may be related to inhibiting the activation of Wnt/β-catenin signaling pathways.