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Background Many studies have reported the presence of Positive Regulatory/Su(var)3-9, Enhancer-of-zeste and Trithorax Domain 2 (PRDM2) downregulation in cancer. However, its potential as a diagnostic biomarker is still unclear. Hence, a systematic review and meta-analysis were conducted to address this issue. Introduction As of 2018, cancer has become the second leading cause of death worldwide. Thus, cancer control is exceptionally vital in reducing mortality. One such example is through early diagnosis of cancer using tumor biomarkers. Having a function as a tumor suppressor gene (TSG), PRDM2 has been linked with carcinogenesis in several solid tumor. This study aims to assess the relationship between PRDM2 downregulation and solid tumor, its relationship with clinicopathological data, and its potential as a diagnostic biomarker. This study also aims to evaluate the quality of the studies, data reliability and confidence in cumulative evidence. Materials & Methods A protocol of this study is registered at the International Prospective Register of Systematic Reviews (PROSPERO) with the following registration number: CRD42019132156. PRISMA was used as a guideline to conduct this review. A comprehensive electronic search was performed from inception to June 2019 in Pubmed, Cochrane Library, ProQuest, EBSCO and ScienceDirect. Studies were screened and included studies were identified based on the criteria made. Finally, data synthesis and quality assessment were conducted. Results There is a significant relationship between PRDM2 downregulation with solid tumor (RR 4.29, 95% CI [2.58–7.13], P |