The current study aimed to evaluate the in vitro scolicidal action of pumpkin seed oil (PSO) alone or combined with nitazoxanide (NTZ). Also, the clinical efficacy and protective effect of PSO alone or combined with NTZ against complications of secondary hydatidosis were detected in vivo. Collected protoscolices (PSCs) from camels were exposed to concentrations of 10 μg/ml and 750 mg/ml from NTZ and PSO, respectively or their combination for 5-,15-, 30- and 60-min in vitro. Viability reduction and ultrastructure changes were evaluated by light and scanning electron microscopy. Fifty-six rats were divided into eight equal groups: Groups1,2, negative and vehicle; group 3, received 500 PSCs of hydatid cyst intraperitoneally; group 4, received NTZ at a dose of 50 mg/kg BW; group 5, received PSO at a dose of 250 mg/kg BW; groups 6-8, animals infected as group 3 and treated as groups 4, 5 and their combination, respectively. Treatments continued orally for 14 days then samples collected for anti-echinococcus immunoglobulin G and cytokines estimation, hemato-biochemical study and histopathological examination. The combination treatment in vitro provoked greater scolicidal action and ultrastructural alterations in PSCs compared to the monotherapy. The combined treatment group produced effective scolicidal action in vivo, inhibited inflammatory condition, induced immunomodulatory effect and improved the alterations in hemato-biochemical parameters and histopathological picture in examined tissues. In conclusion, this treatment strategy may provide a new efficient and safe way for echinococcosis treatment in the future and may recommend the use it before, during and after surgical removal of hydatid cysts.