Abstract: Objective To explore the efficacy and safety of telbivudine and tenofovir in the treatment of the patients with chronic hepatitis B during pregnancy and its effect on reducing mother-to-child vertical transmission of HBV. Methods From January, 2016 to December, 2017, 80 HBeAg positive pregnant women, with HBV DNA>10⁶ IU/ml, were randomly divided into two groups (n=40). The patients in the control group received telbivudine in the middle and late stages, while the patients in the research group received tenofovir in the middle and late stages. The medicines were withdrawn until three months after postpartum. All the newborns were given blockade therapy. Alanine aminotransferase (ALT) and HBV-DNA were detected before the treatment and delivery. The HBeAg, HBsAg positive and HBV DNA ≥ 100 IU/ml were detected when babies were born, seven months and one years after the birth. The biochemical indexes, virology response, infant growth and development, mother to child transmission of hepatitis B, and adverse reactions were observed and compared between the two groups. Results Before the delivery, the HBV DNA and ALT levels in the research group were less than those in the control group, the ALT normalization rate (97%) and the negative conversion rate of HBV-DNA (95%) in the research group were higher than those in the control group, the differences were statistically significant (P<0.05). There were no significant differences in the Apgar score, weight between the two groups of childbirth. The success rate of neonatal interruption in the research group (100%) was higher than that in the control group (72.5%). One year after the birth of infants, the serum HBeAg, positive rate of HBsAg and HBV DNA 100 IU/ml in the research group were lower than those in the control group, there was no obvious adverse reaction between the two groups of mothers and infants. Conclusion Tenofovir can reduce maternal serum HBV DNA levels of hepatitis B infection, improving liver function, the blocking rate of vertical transmission, reducing infant HBV infection rate, having no significant adverse reactions, good safety, and it was worth popularizing.