The therapeutic management of melanoma, the most aggressive form of skin cancer, remains challenging. In the search for more effective therapeutic options, metal-based complexes are being investigated for their anticancer properties. Cisplatin was the first clinically approved plati-num-based drug and, based on its success, other metals (e.g. gold) are being used to design novel compounds. In the present work, the antimelanoma potential of a new organometallic cy-clometalated Au(III) complex [[Au(CNOxN)Cl2] (CNOxN = 2-(phenyl-(2-pyridinylmethylene)aminoxy acetic acid))] (ST004) was evaluated in vitro and in vivo. Furthermore, this new gold-based complex was associated to liposomes with the lipid composition DMPC:DOPE:DSPE-PEG (50:45:5) to overcome solubility and stability problems, as well as to promote accumulation at melanoma sites and maximize the therapeutic effect. Devel-oped liposomal formulations showed a low mean size (around 100 nm), high homogeneity (PdI100 μM). Cell cycle analysis revealed an arrest in G0/G1 phase by Free-ST004 in all cell lines. In turn, LIP-ST004 led to a G0/G1 halt in B16F10, and to an arrest in S phase in A375 and MNT-1 cells. Preliminary mechanistic studies suggest gold-based inhibition of glycerol permeation through aquaglyceroporin 3 (AQP3) in human red blood cells used as a model. The proof-of-concept of the antimelanoma properties of LIP-ST004 was obtained in subcutaneous and metastatic murine melanoma models. In the latter, results showed a significant reduction on lung metastases in animals receiving LIP-ST004, com-pared to free gold complex and DTIC. Globally, this study highlights the antimelanoma potential of a new gold-based complex.