The present study aimed to the preparation of bioactive Quercetin copper-conjugated bromelain nanoparticles in gel form for the treatment of skin cancer. The Quercetin nanoparticles have been prepared by using polyacrylamide and Tween 80 as surfactant. Synthesized nanoparticles were evaluated for drug entrapment efficiency and particle size and further proceed to prepare metallic nanoparticles. Quercetin copper nanoparticles have been prepared by dissolving copper nitrate in 50 ml deionized water heated to 60-70ºC in a conical flask. Copper nitrate solution was added dropwise in the Quercetin nanoparticle till the color changed under a magnetic stirring followed by centrifugation at 6000 rpm for 10 min. Pellet was separated from the supernatant, and washed with deionized water. Dried at room temperature and kept at -20ºC. In the next phase, the Quercetin copper nanoparticle was bioconjugated with bromelain and subsequently evaluated for entrapment efficiency, particle size, zeta potential, and XRD study. Bioconjugated Quercetin-loaded copper nanoparticles were dispersed in Carbopol 934 gel base and characterized by measuring pH, viscosity, gel strength, extrudability study, and spreadability. In vitro, release studies & skin permeation have been determined using Franz diffusion cell. The MTT assay has been analyzed against HaCaT (immortalized human keratinocytes) cell lines, to determine their anti-cancer potentials. The conjugated formulation was found to decrease cell viability and higher skin targeting efficacy in in-vitro studies. The metal-conjugated gel of Quercetin is an efficient and economic approach for the treatment of skin cancer.