The research included the formation of chalcone derivatives, which are organic materials with biological importance, on which this research is based. The Chalcone derivatives were synthesised from the Claisen-Schmidt condensation reaction. Compounds I-III were synthesised by reacting p-aminoacetophenone with (4-methylbenzaldehyde,2,3-dimethylbenzaldehyde, and cinnamaldehyde), respectively, in an ethanolic solution of KOH (30%). Chalcones were characterised byFourier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance (1H NMR). The cytotoxicity effect was demonstrated in human melanoma cells A-375 and HdFn normal cells, and the MTT results showed that the cytotoxicity of Chalcone derivatives was greater than HdFn cells. The ability to use Chalcone derivatives as sunscreen showed a promising result.