Objective To observe the efficacy and side-effect of alternative and combined use of albendazole (ABZ) and praziquantel (PQT) in the treatment of human echinococcosis in Tibetan herdsmen. Methods Patients with liver echinococcosis were diagnosed by abdominal B ultrasound and sero-antibody detection in Ruo Ergai and Rangtang counties, Sichuan Province. The patients were randomly divided into two groups and were alternatively administered with oral ABZ and PQT (ABZ+PQT treatment group) or ABZ alone (ABZ control group). The ABZ+PQT group patients were given with 15 mg/kg ABZ daily dosed in 2 times for consecutive 25 days, followed by an alternative single dose of 40 mg/kg PQT for 5 days. The treatment was continued with the two regimes alternatively, a 3-month dosing was defined as a treatment course, with no intervals between courses. For the ABZ group, patients were given with ABZ at a total daily dose of 15 mg/kg dispensed in two times for 3 months, followed by a new treatment course after an one-week intermittence. All the patients were treated for 2 years. During the treatment courses, all patients received B ultrasound examination, serum test for IgG antibody against Echinococcus metacestode and liver function monitoring, every 6 months. To understand the adverse effects of the drugs on liver function, questionnaire survey was performed. Results A total of 97 clinically diagnosed echinococcosis cases were for treatment and following up in this study, having 55 cases in the ABZ+PQT group, of them, 31 were cystic echinococcosis (CE) and 24 alveolar echinococcosis (AE) cases. In the ABZ control group, 47 patients (22 CE, 20 AE) were included. In the ABZ+PQT group, the cure rate and effective rate were 19.4% (6/31) and 58.1% (18/31) for CE cases; and 12.5% (3/24) and 50.0% (12/24) for AE cases, respectively. In the ABZ group, the cure rate and effective rate were 9.1% (2/22) and 18.2% (4/22) for CE cases; and 5.0% (1/20) and 20.0% (4/20) for AE cases, respectively. The serum anti-Echinococcus IgG antibody titer in the two groups during treatment courses did not show statistical changes. The serum anti-Echinococcus antibody A₄₅₀ value was 0.39 ± 0.06 in the ABZ+PQT group before treatment, and elevated to 0.45 ± 0.05 after 3 months of treatment, but reduced to 0.39 ± 0.07 after 12 months of treatment and stayed stable afterwards. The antibody change profile in the ABZ group was similar to that in the ABZ+PQT group. The antibody A₄₅₀ value was 0.41 ± 0.07 before treatment, elevated to 0.43 ± 0.08 after 3 months of treatment and turned down to 0.39 ± 0.07 after 12 months of treatment. The A₄₅₀ values of sero-antibody varied significantly at different time points of the treatment course. The general side effects occurred in 23.7% (23/97) of patients, among them, 8 (34.8%) cases were from the ABZ+PQT group, while the other 15 cases (65.2%) were from the ABZ group, displaying largely as mild side effect of gastrointestinal discomfory; severe effects occurred as impairment of liver function. In 3 months of treatment, 6 cases (1 case in the ABZ+PQT group, 5 in the ABZ group) showed elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which then reduced to normal level upon following up period. Conclusion The effective rate of ABZ+PQT group regime for CE and AE was higher than that of ABZ group; adverse effects occurred in the ABZ+PQT treatment group significantly less frequently than in the ABZ treatment group; the changes of serum IgG antibody can not reflect the actual lesion progression.