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Purpose: To study the effect of overexpression of Rac1 on the radiosensitivity of transplanted nasopharyngeal carcinoma (NPC) in nude mice, and the mechanism involved. Methods: Forty Lucky SPF-grade male thymus-free nude mice were used. Mice were divided into 4 groups: overexpression control, overexpression Rac1, Rac1 inhibition, and inhibition control groups, each with 10 mice. The prepared cell lines were treated with 6 MV x-ray. Before and after radiation, the growth of tumors in each group was monitored. Histomorphological images of nude mice tumors were obtained using hematoxylin and eosin (H&E) stains. Protein expressions of p67, P47, and Rac1 were evaluated bu Western blotting. Results: Transplanted tumor growth slowed down after 20 days. Growth rate was significantly higher in Rac1 and Rac1 overexpression groups than in overexpression and inhibition control groups (p < 0.05). Overexpression of Rac1 resulted in more cell necrosis, incomplete cellular structure, severe nuclear fragmentation, nuclear pyknosis, and cytotoxic red staining in endoscopic tumor tissues (p < 0.05). There were significantly lower expression levels of p67, P47, and Rac1 in Rac1 invasion group than in invasion control and overexpression control groups, while the expression levels of p67 and P47 were significantly higher in overexpression Rac1 group and IR overexpression Rac1 group than in inhibition control (p < 0.05). However, concentrations of p67 and P47 were significantly higher in overexpression Rac1 and IR overexpression Rac1 groups than in inhibition control mice. Conclusion: Rac1 increases the radiosensitivity of NPC xenografts in nude mice via a mechanism related to the regulation of expressions of proteins associated with Rac1/NADPH signaling pathway. Thus, Rac1 is potentially a new target for radio-sensitization of NPC.