The present study was conducted to evaluate the antitumor effect of silver nanoparticles and Alpha-lipoic acid and their combination against 1,2-dimethylhydrazine (DMH-) induced colorectal carcinogenesis in experimental rats. Fifty Male wistar albino rats were divided into five groups. Group (1): negative control group, group (2) colorectal cancer induced rats (CRC) (positive control), group (3): CRC group treated with silver nanoparticles (CRC+AgNPs), group (4): CRC induced rats treated with Alpha-lipoic acid (CRC+ALA) and group (5): CRC induced rats treated with combinations (CRC+ AgNPs + ALA). The obtained biochemical results revealed significant reduction in serum transforming growth factor-β (TGF-β), Tumor necrosis factor α (TNF-α), C – Reactive Protein (CRP), carcinoembryonic antigen (CEA) and colon cancer specific antigen-4 (CCSA-4) levels in CRC induced group treated either with silver nanoparticles or alpha-lipoic acid and their combinations compared to CRC induced group. Regarding gene expression, we found significant down regulation in K-RAS gene expression with treatment with either AgNps or ALA or their combinations comparing to untreated group. Histopathological study greatly supports these results. In Conclusion; the present study highlighted the antitumor effect of AgNPs, ALA and their Combination in ameliorating CRC induced experimentally through its potential anti-inflammatory effect.