Abstract Gastric cancer is a pathological condition induced by bacteria Helicobacter pylori. Targeting the key virulence factors of H.pylori causing gastric cancer is one such promising method for treating gastric cancer. Recently research has been focussed on analysing the adrenergeric, cholinergeric and anticancer properties of their venom proteins. Testing the anticancer activity of the lethal proteins in the venom of P.volitans not only provides a bioactive compound for cancer treatment but is also helpful to eliminate the ecological imbalance caused by this fish in marine environment. This study is focused on an in silico approach using Z-dock for analysing the bioactive prospective of the venom proteins of P.volitans against the key virulence proteins of H.pylori responsible for inducing cancer. Our in silico docking study using computational model of the venom proteins and H.pylori proteins has displayed the possible interactions between these proteins. The results revealed that the venom proteins of P.volitans hyaluronidase and PV toxin a effectively interacts with H.pylori proteins Cag A, Cag L, GGT, Cag D and Urease and may be promising proteins in cancer therapy.