Objective To explore the possible mechanism of action of telomerase in hepatic precancerous lesions, and the regulatory effect of a Chinese medicine prescription HU Qi Shan (HQS) and its principal drug mistletoe alkali on the telomerase activity in rat liver tissues. Methods Rat model of hepatic precancerous lesions was established by Solt-Farber two-step protocol. The model rats were randomly divided into 5 groups, including the model group, high-dose HQS[8 g/(kg·d)] group, low-dose HQS[4 g/(kg·d)] group, and mistletoe alkali[8 mg/(kg·d)] group. γ-Glutamy-transpeptidase (γ-GT) was analyzed by immunohistochemistry. AFP was detected by immunofluorescence technique.The telomerase activity was detected using a quantitative telomerase detection kit. The expression of NF-κB P65 was detected by immunohistochemistry. The cytoplasmic protein IκB-α was detected by western blotting. Results After treated with HQS and mistletoe alkali, the areas of γ-GT-positive foci and number of AFP-positive cells in the liver tissus were significantly decreased than those of the model group (P<0.05 for both), the telomerase activity was decreased, the number of NF-κB P65-positive cells was also decreased (P<0.05), whereas the intracytoplasmic expression of IκB-α proteins was significantly increased (P<0.05). Conclusions HQS and mistletoe alkali can suppress the telomerase activity. Its possible mechanism may be through inhibition of the over-expressed apoptosis-related genes such as NF-κB P65 and increase the expression of IκB-α decreasing the telomerase activity.