This study aims to investigate the clinical efficacies of initial combined application of Lamivudine (LAM) and Adefovir Dipivoxil (ADE) in treating the Decompensation Stage of Hepatitis B-caused Cirrhosis (DS-HBC). 200 DS-HBC patients treated were selected and randomly divided into the Observation group (OBS) and the Control group (CON): The observation group was administrated the initial combined therapy of LAM and ADE, and the control group was co-administrated LAM after ADE-resistance appeared. Such indexes as HBeAg/HBeAb seroconversion, HBV-DNA outcome, Child- Pugh score, and liver functions between the two groups after 6 and 12-month treatment were then compared. The HBeAg/HBeAb seroconversion in OBS was higher than CON (6 month: 37% vs. 19%, 12 month: 69% vs. 43%), the HBV DNA negative-conversion rate was also higher (6 month: 38% vs. 21%, 12 month: 88% vs. 54%), the Child-Pugh score was significantly lower than CON (6 month: 8.9 ± 0.5 vs. 9.2 ± 0.5; 12 month: 7.5 ± 0.4 vs. 8.7 ± 0.9), and the liver functions were better than CON. The differences in the above results between the two groups were statistically significant (P<0.05). The clinical efficacies of initial combined application of LAM and ADE in treating DS-HBC were better those of second-line combined therapy, so it was worthy of promotion.