Objective: To evaluate the clinical efficacy of percutaneous transhepatic stone disintegration and extraction in treatment of hepatolithiasis under B ultrasound positioning and X-ray guidance. Methods: Patients with intrahepatic stones admitted from June 2015 to February 2016 were selected, and then were randomly designated to observational group and control group, with 30 cases in each group. Patients in observational group underwent percutaneous transhepatic stone disintegration and extraction under B ultrasound positioning and X-ray guidance, and those in control group underwent percutaneous transhepatic stone disintegration and extraction under X-ray guidance alone. The relevant clinical variables and the quality of life between the two groups at 6 months after operation were compared. Results: In observational group compared with control group, the length of hospital stay and time to bowel function recovery showed no significant difference (both P>0.05), but operative time (69.46 min vs. 158.67 min), intraoperative blood loss (35.15 mL vs. 102.76 mL) were significantly reduced, the number of cases with surgical success (30 vs. 25) was significantly increased, the number of cases with residual stones (0 vs. 6) and early recurrence (0 vs. 4) were significantly decreased, the incidence of postoperative acute pancreatitis, acute cholangitis, bile leakage and hemorrhage were all significantly decreased, and the scores for all parameters of the SF-36 at 6 months after operation were all significantly elevated (all P<0.05). Conclusion: Percutaneous transhepatic stone disintegration and extraction under B ultrasound positioning and X-ray guidance is a safe, effective and convenient method of treatment for hepatolithiasis. It also has advantages of accurate location, high stone clearance rate, short operative time and fewer complications.