Background <p>This meta-analysis evaluates the prognostic significance of the Prognostic Nutritional Index (PNI) in colorectal cancer (CRC) patients, focusing on overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS).</p> Methods <p>We conducted a comprehensive literature search across PubMed, Embase, Web of Science, and CNKI. Observational studies reporting hazard ratios (HRs) with 95% confidence intervals (CIs) for survival outcomes based on PNI were included. Pooled HRs were calculated using random-effects models. Heterogeneity, sensitivity, and publication bias were evaluated, and subgroup analyses were performed by region, follow-up duration, and tumor stage.</p> Results <p>A total of 43 studies comprising 19,214 CRC patients were included the meta-analysis. 36 studies with 18,231 patients reported the prognostic value of PNI on the OS of CRC, and the pooled HR was 1.89 (95% CI: 1.70–2.10, <i>P</i> &lt; 0.001). This association remained robust across sensitivity analyses, suggesting PNI as a reliable biomarker for risk stratification. Moderate heterogeneity (I² = 32.9%) was observed, which subgroup analyses attributed to study region, follow-up duration, and inclusion criteria for CRC stages. Non-Asian cohorts, studies with shorter follow-up or partial staging and high cut-off value of PNI exhibited reduced heterogeneity. Eleven studies with 5,181 patients reported the prognostic value for DFS, and the pooled HR was 1.31 (95% CI: 0.84–2.03). Nine studies with 2,856 patients were for PFS, and the pooled HR was 1.15 (95% CI: 0.78–1.72), neither reaching statistical significance. Significant heterogeneity was noted for both DFS and PFS across the studies.</p> Conclusions <p>This meta-analysis demonstrates that a low PNI is a robust predictor of poor overall survival in colorectal cancer, particularly in Asian populations and across diverse disease stages. While its prognostic value for DFS and PFS remains uncertain.</p>