Abstract: ObjectiveTo investigate the anti-tumor effects and mechanisms of paeonol (Pae) combined with 5-Fluorouracil (5-Fu) treatment for nude mice loaded human carcinoma of Bel- 7404 cells. MethodsThe tumor model was established by subcutaneously injecting human carcinoma of Bel-7404 cells to right forearm armpits. Nude mice loaded Bel-7404 cells were randomly divided into 4 groups (5 in each group)：①Control group: equal volume NS intraperitoneal injection every two days for 10 days；②5-Fu group: 20 mg/kg, intraperitoneal injection every two days for 10 days; ③Pae group:100 mg/kg, intraperitoneal injection every two days for 10 days; ④Pae+5-Fu group: Pae 100 mg/kg and 5-Fu 20 mg/kg intraperitoneal injection every two days for 10 days. We observed the tumor volumes and weights in each group. Telomerase activity was examined by PCR-TRAP. The expression of human telomerase reverse transcriptase(hTERT) mRNA and protein were analyzed by RT-PCR and Western blot, respectively. ResultsAfter the intervention of Pae, 5-Fu, and their combination therapy, tumor volume and quality of decreased significantly compared with the control group, the tumor-inhibitory rates were 45.32%, 60.79% and 80.22 %, respectively. The results of PCR and Western blot showed that Pae, 5-Fu, and their combination therapy all could significantly suppress telomerase activity,and down-regulate mRNA and protein levels of hTERT. ConclusionPae has a synergistic anti-tumor effect with 5-Fu and the mechanism may be related to reduced telomerase activity and hTERT expression.