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Background: Knee osteoarthritis (KOA) is a common disabling musculoskeletal disorder. Previous studies showed that Tuina manipulation and health care education were effective treatments for patients with KOA. However, there is no evidence to support the use of one intervention over the other. The purpose of this study is to evaluate the effectiveness of Tuina manipulation and health care education for the management of pain and dysfunction in patients with KOA.Methods/Design: This study is a single-centre, two-arm, open-label randomized controlled trial (RCT). A total of 170 eligible KOA patients will be randomly assigned to the Tuina manipulation group or the health education group in a 1:1 ratio. Patients in the Tuina manipulation group will receive a 30-minute 2-step treatment plan, including pain point assessment and manual therapy, which will be performed 12 times in 4 weeks. The health education group will receive 45 minutes of lecture and discussion three times a week for four weeks. The primary outcome is the Knee Injury and Osteoarthritis Outcome Score (KOOS). Secondary outcomes include the McGill Pain Questionnaire (MPQ) and 36-item Short-Form Health Survey (SF-36). The results of this study will help clarify the value of Tuina manipulation and health education as treatments for KOA and will highlight any differences in treatment outcomes.Discussion: The design and methodology of the trial is rigorous and allows the collection of valuable data to assess the efficacy of a specific Tuina regimen for the treatment of KOA. Therefore, the trial will provide a solid foundation for future clinical research on KOA and Tuina therapy.Trial registration: This trial was registered with the Chinese Clinical Trial Registry on 24 February 2020 (ChiCTR2000030154), http://www.chictr.org.cn/index.aspx