The aim of this study was to investigate the anthelmintic effect of pumpkin seeds (Cucurbita maxima) against Aspiculuris tetraptera in naturally infected mice. For this purpose, the natural infection was determined by the cellophane tape (on the anal region), and the centrifugal flotation methods of stool samples in approximately 150 male Swiss albino mice (27 to 35 g). The infected mice (29 animals) were divided into four groups. The animals in the first (G1) and second groups (G2) received water and ethanol extracts of pumpkin seeds orally at the dose suggested for human for 7 days, respectively. The mice in the positive control group (G3) were treated with ivermectin intramuscularly at a dose of 0.2 mg/kg body weight. The mice in fourth groups (G4) received the same amount of serum physiologic orally. The mice were housed in clean polypropylene cages and maintained under standard laboratory conditions at an ambient temperature of 20±2°C with 45% relative humidity and a 12 h light dark cycle. At the eighth day of the study, all animals were killed humanly following inhalation anaesthesia. After euthanasia, the number of parasites in the intestine was counted. Data obtained from the treatment groups were compared using one-way ANOVA. The percentage efficacy of the drugs was calculated. The results of the study showed that the efficacies for water (G1) or ethanol (G2) extracts of pumpkin seed and ivermectin were 81, 85 and 91% compared with the negative control, respectively. These results revealed that pumpkin seed has high anthelmintic activity against nematodes as well as its continued use in traditional medicine for the treatment of helminthiasis.