Rising cases of Non melanoma skin carcinoma (NMSC) and escalating levels of ultraviolet radiations have underlined a profound correlation with the elevating levels of environmental detoriation and increasing health issues. However, the availability of therapeutics has not aided in controlling the recurrence rates of skin carcinoma. Frequent administration of therapeutics with higher chances of facial deformity escalates the patient's treatment expenses. Thus, this study initiates a low cost effective and biodegradable therapy by exploring four formulations with combinations of silver nanoparticles (AgNPs), sericin (isolated from cocoons of Antherea mylitta) and chitosan. Subsequently, various ethosomal formulations were evaluated as a platform for transdermal delivery vehicle for efficient skin intervention therapeutics. Characterization using UV visible spectroscopy, Dynamic light scattering, Fourier Infrared spectroscopy, X-ray dispersion, Transmission electron microscopy, Fluorescence assisted cell sorting and in vitro studies were done and it was inferenced that equal combination of AgNPs and sericin facilitated to combat the morphological and cellular deformation of the epidermoid A431skin carcinoma cells. The overproduction of superoxide (O and nitric oxide (NO) radicals consequently depolarized the mitochondrial membrane potential triggering apoptosis and necrosis. The in vivo experiments exhibited the stimulation of IgM secretion with T cell-mediated immune response. Therefore, this study proposes a novel approach for treatment of NMSC using biocompatible formulations delivered through ethosomes.