Most basal cell and squamous cell skin cancers are caused by repeated and unprotected skin exposure to ultraviolet (UV) rays from sunlight. Incidence of skin cancer is rapidly increasing worldwide and it causes public health problems. The treatments for local skin cancers include mostly surgery, usually leaving a scared tissue or chemotherapy and radiations for melanoma, and oral and topical medication. We aim to develop an efficient personalized RNAi based topical treatment for skin cancer patients which is based on two technologies- one is Tissue Ex-vivo assay (TEVA) where we utilize suitable RNAi to target particular gene to downregulate such genes which are highly expressive in tumor cells, thus we can reduce tumor volume and the other technique is ultrasound based-technology that allows modified polysaccharide/RNAi nano-complexes to penetrate efficiently into the skin and enhance therapeutic effect. We have checked the penetration of Cy5 tagged siRNA into the 2x2x2 mm3 Cal33 CDX chunks in presence of JETPRIME transfection reagent after 24 hours. In future, we are aiming to check the silencing effect of different siRNAs into the chunks and developing a broad siRNA screening system for better tailoring systemic personalized treatment. This screening system will be utilized to build a topical treatment using ultrasound for the better penetration of modified polysaccharide/RNAi nano-complexes for skin cancer patients.