Background <p>Epstein-Barr virus (EBV) is a well-recognized oncogenic virus associated with the development of various malignancies. In North Africa, EBV-related cancers, such as nasopharyngeal carcinoma, gastric cancer, and lymphomas, present a significant health challenge due to their high mortality rates. Despite the common occurrence of these malignancies, the prevalence and impact of EBV infection in this context remain largely unexamined. Addressing this knowledge gap is crucial for understanding the virus’s role in cancer pathogenesis and for informing effective prevention and treatment strategies.</p> Methods <p>Electronic databases will be searched for literature published up to 2025 using a Boolean search approach combining common terms and Medical Subject Headings (MeSH) for EBV infection, cancer, and North Africa. The review will only include studies carried out in North Africa that assess the prevalence of EBV infection in patients with cancer. Using the Joanna Briggs Institute (JBI) critical appraisal tools, the quality and potential risk of bias of all selected full-text articles will be evaluated.</p> Discussion <p>This protocol outlines a systematic review and meta-analysis aiming to evaluate the prevalence of EBV infection in cancer patients in North Africa to better understand its role in the region’s cancer burden. Insights from this study will support improved prevention, early detection, and more personalized treatment strategies, ultimately aiding the reduction of cancer mortality in the region.</p> Systematic review registration <p>This protocol has been published in the PROSPERO International Prospective Register of Systematic Reviews (<a href="http://www.crd.york.ac.uk/PROSPERO">http://www.crd.york.ac.uk/PROSPERO</a>), under the registration number CRD42024594373.</p>