Objective: Dermal delivery of Doxorubicin (Dox) would be an ideal way in maximising drug efficiency against skin cancer accompanying with minimising side effects. We investigated the potential of Dox-loaded Solid lipid nanoparticles (SLNs) for topical delivery against skin cancer.Methods:In vitro and in vivo cytotoxicity of optimised formulation were evaluated on murine melanoma (B16F10) cells by MTT assay and melanoma induced Balb/C mice, respectively. Animal study followed by histological analysis.Results: Optimised formulation showed mean particle size and encapsulation efficiency (EE) of 92nm and 86% w/w (0.86% w/w value of encapsulated Dox in the lipid matrix), respectively. FTIR experiment confirmed drug-lipid interaction interpreting the observed high EE value for Dox. In vitro and in vivo results indicated the superiority of cytotoxic performance of Dox-loaded SLN compared to Dox solution.Conclusion: Our findings may open the possibilities for the topical delivery of Dox to the skin cancerous tissues.