Background: Thymoquinone (TQ), the main constituents of the volatile oil from Nigella sativa seeds and it is reported to protect laboratory animals against chemical toxicity and induction of carcinogenesis. This study was undertaken to investigate the potential protective and curative effect of TQ on Ehrlich solid carcinoma cells (ESC) inoculated mice-induced carcinogenesis. Material and methods: (50) Swiss albino mice were divided into five groups. Control group, Thymoquonone group: animals of this group were orally treated with TQ (10 mg/kg/day) for 4 weeks, Ehrlich Carcinoma group : animals of this group were inoculated intramuscularly with 0.2mL Ehrlich Ascites Carcinoma (2.5×106 cells) in the right thigh of the lower limb, Thymoquinone and Ehrlich carcinoma group: animals of this group were pre-treated with TQ for 14 days then inoculated with (EAC) and Ehrlich Carcinoma and Thymoquinone group : in this group animals were inoculated with EAC then after 8 days received TQ orally for a month. Morphological, Molecular as well as histopathological and ultrastructural changes were examined. Results: Our results revealed that TQ showed a significant anti-tumor activity in ESC bearing mice represented by a reduction in tumor weight and volume. Flow cytometric analysis illustrated that the level of apoptosis is significantly decreased in ESC inoculated group. Otherwise, TQ+ESC and ESC+TQ groups showed a highly significant increase in apoptosis G0/1 peak. The level of P53 protein expression showed a significant decrease in ESC inoculated group, and this decrease was ameliorated in TQ+ESC and ESC+TQ groups when compared to ESC inoculated group. Histopathological observations showed a reduction in tumor size after treatment with Thymoquinone and this tumor was found to be discontinuous and fragmented with slowly growing. Conclusion: our results revealed that TQ has potential benefits in the prevention of the onset and progression of solid tumor model in mice.