Abstract Objective In order to approach the possible mechanism of action ,we study that how is HQS to regulate the telomerase activation in the hepatocarcinogenesis. Methods Solt-Farber two-step test model of the liver lesion precancerous was established in rats. The rats were divided into 5 random groups, including model group, large dose of HQS [8g/(kg•d)]group, small dose of HQS [4g/(kg•d)]group, mistletoe alkali group [8mg/(kg•d)] and normal group. r-Glutamy-transpeptidase(γ-GT) were determined with histochemical methods; AFP was detected by immunofluorescence; the telomerase activity was investigated by Quantitative Telomerase Detection Kit（QTD Kit）; the expressions of the nuclear factor-kappa B(NF-kB)P65 were detected by immunohistochemistry; the cytoplasmic protein IκB-α was detected by Western blotting . Results The results of experiment showed that after treated with HQS and mistletoe alkali, which the areas of -GT positive foci and the positive numbers of AFP are significantly decreased compared with that of the model group(P0.05); at the same time the telomerase activity have the similar tendency results comparing to the AFP; The NF-κB P65 expressed the similar tendency compared with the telomerase activity ;whereas the expressions of the IκB-α in the cytoplasmic proteins have the contrary results compared with the expression of the NF-κB P65. Conclusion HQS and mistletoe alkali can inhibit the areas of -GT positive foci and decrease the positive numbers of AFP and promote the differentiation of the hepatocyte from juvenile to mature in the progress of the hepatocarcinogenesis; HQS and mistletoe alkali can decrease the expression of the telomerase activation, its possible mechanism is that it maybe inhibit the over-expression of the related apoptosis genes such as NF-κB P65 and increase the expression of IκB-α to decrease the expression of telomerase activity.