Currently, the minimally invasive "Step-up" surgical strategy is still the main treatment for infected pancreatic necrosis (IPN). However, indiscriminate implementation of the "Step-up" strategy can lead to increased numbers of operations and prolonged hospital stay. The "Step-up" approach is not appropriate for some patients due to unavailabilty of a safe puncture path. Therefore, we developed the "One-step" surgical approach to treat IPN, which is safety. However, there is still a lack of comparison of the short and long-term efficacy between the "One-step" and "Step-up" approach. Consequently, we are conducting this clinical trial to provide a reference for IPN treatment.This is an ongoing, single-center, randomized controlled trial of patients with IPN. The total sample size required for the trial (May 2021-December 2023) is approximately 128 patients. Patients will be randomly assigned to either an experimental group (One-step) or a control group (Step-up) at a ratio of 1:1 using the block randomization method. We used the case report forms and electronic data capture systems to obtain demographic information, preoperative laboratory examination, auxiliary examination results, surgery data, postoperative recovery outcomes, and follow-up outcomes. The patients will be followed up for 2 years after surgery. The primary endpoint is a composite endpoint, consisting of mortality and severe complications. The secondary endpoints include the incidence of organ dysfunction, the number of surgical procedures, mortality (the incidence of death in hospital and deaths within 30 days of discharge), hospital stay, intensive care unit stay, hospitalization costs, perioperative inflammatory marker changes, and short-and long-term complications.Compared with the "Step-up," the "One-step" minimally invasive surgery can significantly reduce the number of operations, reduce the length of hospital stay and hospitalization costs without increasing the incidence of composite endpoint events, and has better short- and long-term efficacy and safety. Additionally, there was no statistically significant difference in perioperative complications and mortality between "Step-up" and "One-step". This study will assist with the formulation of an effective and scientific "One-step" minimally invasive treatment strategy for IPN, and an understanding of this technique will facilitate clinical decision-making for IPN. Trial Registration ChiCTR2100044348. Trial status: Ongoing.© 2022. The Author(s).