Background: Advances in early detection and treatment of colorectal cancer (CRC) has seen marked improvements in recent years. However, it is still the third leading cause of cancer-related deaths worldwide. Although there are studies reporting the significance of miRNAs in stage II colorectal cancer, there is no known comprehensive study utilising collective data from multiple published studies. Thus, this study will focus on performing a systematic review and meta-analysis using published data to identify and underline multiple miRNA targets, with regard to disease prognosis in stage II CRC patients. Methods: The systematic review will be reported according to the Preferred Reporting Items for Systematic Review and Meta- Analysis (PRISMA) guidelines, 2015 statement. The required articles will be obtained via a search of bibliographical databases such as Cochrane Library, EMBASE, MEDLINE, PubMed, and Web of Science. A set of keywords in multiple permutations will be used for the search. The reference lists of included studies will also be manually searched to further increase the robustness of the search results. The systematic review will primarily be done via a literary synthesis. Results: Quantitative data synthesis will be based on estimated effect across the studies with forest plots generated to observe pooled outcome measures. A fixed or random-effect model of meta-analysis will be used depending upon the heterogeneity observed between studies. Subgroup analysis will be carried out depending on the availability of sufficient clinical data. Conclusion: Based on the systematic review and meta-analysis results of this study, the possible miRNAs could be predicted toward the prognosis of stage II colorectal cancer, and specific miRNAs may perhaps be considered as a biomarker and therapeutic target for this malignancy. Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.