Background <p>Given limited and conflicting data, this systematic review and meta-analysis investigate the impacts of statin use on survival outcomes and adverse events in patients with cancer receiving radiotherapy.</p> Methods <p>A comprehensive search of MEDLINE, EMBASE, Web of Science, Scopus, and PubMed (January 2000 to June 2024) included studies on adults (≥ 18 years) with histologically confirmed cancer receiving oral statins during radiotherapy. Overall survival (OS) rates and radiotherapy-related adverse effects were compared between statin users and non-users using odds ratios (ORs) and 95% confidence intervals (95%CIs). Meta-regression explored the effects of cancer type and statin intensity on OS rates, reported as coefficients (β) and 95%CI.</p> Results <p>Of 21 studies (19 cohort studies and two randomized trials), OS rates did not significantly differ between statin users and non-users (OR: 1.29; 95%CI: 0.99, 1.69) or by statin intensity (β: 0.20; 95%CI: -1.22, 1.62; <i>p</i> = 0.60), but significantly by cancer types (β: -0.29; 95%CI: -0.45, -0.13; <i>p</i> &lt; 0.01). Statin use was associated with improved survival in oesophageal squamous cell carcinoma (SCC), head and neck SCC, glioblastoma, and prostate cancer, but with reduced survival in non-small cell lung cancer (NSCLC) and brain metastases. Statin users had a higher risk of major adverse cardiac events (OR: 2.22; 95%CI: 1.38, 3.59) in NSCLC and ≥ grade 2 mucositis (OR: 26.00; 95%CI: 4.09, 165.10) in head and neck squamous cell carcinoma but lower risks of ischemic stroke (OR: 0.80; 95%CI: 0.67, 0.95) in nasopharyngeal carcinoma and rectal toxicity (OR: 0.45; 95%CI: 0.23, 0.88) in prostate cancer.</p> Conclusions <p>Survival outcomes did not significantly differ by statin use or intensity but varied by cancer type. Statin users had lower risks of ischemic stroke and rectal toxicity. Further studies are needed to control for confounding biases.</p> Trial registration <p>PROSPERO registration CRD42023487336.</p>