A number of polysaccharides exhibit pharmacological activities. Polysaccharides derived from Inonotus obliquus (PLIO) appear to have various potential pharmacological properties, including anti‑tumor activity. However, the molecular mechanisms underlying these properties remain to be elucidated. The present study investigated the anti‑metastatic potential of PLIO and the underlying signaling pathways in B16‑F10 murine melanoma cells using the MTT colorimetric assay, in vitro migration and invasion assays, and flow cytometric and western blot analyses. PLIO inhibited the invasion of B16‑F10 cells and suppressed the expression of matrix metalloproteinases. PLIO treatment inhibited nuclear factor‑κB (NF‑κB) nuclear translocation in B16‑F10 cells. In addition, PLIO treatment inhibited the phosphorylation of c-Jun N‑terminal kinases and AKT. These results suggest that PLIO may suppress the invasion of highly metastatic melanoma cells via inhibition of the AKT/NF-κB signaling pathways.