Background: LipoxinA4 (LXA4) is an anti-inflammatory lipid mediator which was recently proposed to have antitumor potential. However, the therapeutic effect of LXA4 in melanoma is still unclear. This work aimed to investigate the function of LXA4 and its analog in melanoma invasion through in vivo and in vitro experiments. Methods: The expression of the LXA4 receptor (ALXR) was detected in melanoma tissues and A375 human melanoma cells, using benign melanocytic nevi tissues and human melanocytes as negative controls, respectively. The invasive and apoptotic abilities of A375 cells in the presence or absence of LXA4 were examined by cell invasion assay and flow cytometric analysis. Finally, mice melanoma models were established, and the antitumor effects of BML-111 [5(S), 6(R)-7-trihydroxymethyl heptanoate], an agonist of ALXR, were examined in vivo. Results: ALXR was abundantly expressed in human melanoma tissues. The ALXR messenger RNA (mRNA) and protein expression levels were higher in A375 melanoma cells than in the controls (P<0.05). LXA4 could significantly attenuate the invasion ability of A375 cells (P<0.05). This trend was further enhanced by BML-111, which tended to control the tumor development in A375 melanoma models. Conclusions: LXA4 and its analog BML-111 exert antitumor effects in vivo and in vitro, and may be potential therapeutic options for patients with invasive melanoma.