Abstract: Objective To investigate the effect of minimally invasive percutaneous plate osteosynthesis (MIPPO) in the treatment of humeral shaft fracture. Methods Total 16 patients with humeral shaft fracture admitted to the Department of Orthopedics, the First Affiliated Hospital of Bengbu Medical College from February 2015 to December 2019 were randomly divided into observation group and control group. The observation group was treated with MIPPO technology, and the control group was treated with open reduction and internal fixation with plate. The operation time, bleeding volume, incision length, postoperative complications, the time of fracture healing and upper extremity function in the last follow-up were compared between the two groups. Results The operation time, incision length, and bleeding volume in the observation group were lower than those in the control group with statistically significant difference. The hospitalization time in the observation group was lower than that in the control group, but the difference was not statistically significant. In the observation group, all cases were going without complications happened, such as infection, radial nerve injury. Otherwise in the control group, there were 1 case of incision fat liquefaction, 1 case of radial nerve injury symptoms after operation, all improved after symptomatic treatment. In the two groups, all fractures were healed, but the average healing time of the observation group was lower than the control group with the statistical significant difference. At the last follow-up, the DASH score of the observation group were lower than the control group with the statistical significant difference. Conclusion MIPPO is an effective method for the treatment of humeral shaft fracture, and worthy of clinical application.