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This study was conducted to investigate the chemopreventive effect of black cumin seeds oil (Nigella sativa), p53 & H-Ras gene expression, and CD8 count in 80 dimethylbenzanthracene (DMBA)-induced Sprague Dawley mice. The test animals were divided into 8 groups. The normal group was given standard food and drink. The three black cumin seed oil (BCSO) treatment groups received BCSO dosages of 0.25, 2.5, and 5 ml/kgBW/day respectively and they were induced with DMBA. The thymoquinone and tamoxifen groups received 50 mg/kgBW/day thymoquinone and 0.6 mg/kgBW/day tamoxifen respectively and they were induced with DMBA. The DMBA group was induced with 10x20mg/kgBW DMBA for 5 weeks. The solvent group received standard feeding and corn oil solutions. Starting from the third week of treatment, all groups except the normal and solvent groups were given 20 mg/kgBW DMBA twice a week for five weeks. Dissection and data retrieval were conducted at week 27. The chemopreventive effects are measured by nodules incidence, nodul multiplication, total weight, and histopathology. The number of CD8 T lymphocytes is determined by flowcytometer. The p53 and H-Ras gene expression is assessed using densitometry after PCR. The mean intergroup difference was calculated using one way Anova. The results showed that BCSO administration before and during DMBA induction can decrease nodule formation and count, decrease H-Ras gene expression, increase p53 gene expression and CD8 CTLs count. A dose of 0.25 ml/kgBW/day BCSO indicated a chemopreventive effect, increased p53 gene expression and CD8 CTLs count, and decreased H-Ras gene expression, all of which were similar to a dose of 2.25 ml/kgBW/day but safer. It can be concluded that a dose of 0.25 ml/kgBW/day BCSO produces chemopreventive and immunoprotective effects in DMBA-induced SD rats.