Abstract: Objective: To detect the molecular mechanism of radiosensitizing effect of Topotecan on Nasopharyngeal carcinoma mude mice xenografts. Methods: The real-time fluorescence quantitative RT-PCR was used to detect the active mRNA gene level of topoisomerase I in tumor specimens received from radiosensition study. Results: The linear coefficient of correlation of the quantitative standard curve was -0.99. The results in the groups were as follows: the mRNA gene level of Topo-I was 45±2.128 copies/μl in the RT+ TPT group (the radiosensation group), 2112±1.208 copies/μl in the TPT group, 1699 ±1.317 copies/μl in the RT20Gy group and 3559295±1.154 copies/μl in the control group, respectively. The level of Topo-I in RT+ TPT group was the lowest in all the four groups. The statistical significance was shown as compared to the level of TPT group or of RT20Gy group (P<0.05). The statistical significance had also been shown as compared that in each groups with the controls (P<0.05). Conclusion: Administration of topotecan with concurrent radiotherapy can affect and decrease the level of gene activity of topoismerase in the nasopharyngeal-carcinoma cells and this might be an important mechanism of sensitizing effect in the molecular level.