There are approximate more than 100 viruses comes under human Papillomavirus family and 40% of them are easily transmitted through sexual contact, from skin and mucous membrane of infected people. E6 protein of HPV mainly acts as an oncoprotein by stimulating the destruction of many host cell key regulatory proteins. The main aim of present study is to identify the potential natural inhibitors against E6 protein. Through literature search 28 inhibitors were selected and analyzed molecular descriptor properties, applied Lipinski’s rule of 5 to select only druglikeness ligands, thus 12 inhibitors remain. The docking was performed by Auto Dock and calculates lowest binding energy to select top hits. Curcumin and Dihydroisocoumarin bind more efficiently to target protein. Therefore, the outcomes of present study may provide new insights in understanding of selected twelve natural inhibitors which can be potential candidates against oncoprotein (E6).