Objective: To investigate the clinical application value of three-dimensional (3D) laparoscopic liver resection for primary liver cancer. Methods: Using prospective non-randomized controlled design, 90 patients with primary liver cancer admitted from March 2012 to October 2015 were enrolled and underwent 3D high-definition laparoscopic liver resection (3D group, 48 cases) and traditional two-dimensional (2D) laparoscopic liver resection (2D group, 42 cases) respectively. The main clinical variables between the two groups of patients were compared. Results: The preoperative data were comparable between the two groups of patients. The surgical procedure, intraoperative blood loss, volume of transfusions, incidence of postoperative complications, length of hospital stay and hospitalization costs showed no statistical difference between the two groups (all P>0.05), but the operative time in 3D group was significantly less than that in 2D group (522 min vs. 566 min, P=0.001). Conclusion: 3D high-definition laparoscopic liver resection is helpful in precise dissection and shortening operative time, without increasing associated injuries and total hospitalization costs. So it is a safe, effective, economical and minimally invasive procedure.