Background <p>This study aims to evaluate the role of C-reactive protein (CRP) in necrotizing enterocolitis (NEC) diagnosis and prognosis through a systematic review and meta-analysis.</p> Methods <p>A comprehensive search was conducted across PubMed, Cochrane Library, Embase, and Web of Science databases to identify relevant studies on CRP and NEC. Outcomes included correlations between CRP levels and NEC occurrence, surgical intervention, severity, and intestinal strictures.</p> Results <p>A total of 30 studies were included in the analysis. Data from categorical variables indicated a significant positive association between CRP and the incidence of NEC (OR: 3.5, 95% CI: 2.23–5.49), while continuous variables revealed a significant difference in CRP levels between the NEC and non-NEC groups (SMD: 2.61, 95% CI: 1.72–3.5). Elevated CRP levels were significantly correlated with an increased risk of surgery, with a notable difference in CRP levels between the surgical and non-surgical groups. CRP levels were also positively associated with the risk of NEC progression, and a significant difference was observed between the progression and non-progression groups. Besides, a significant difference in CRP levels was observed between the stricture and non-stricture groups. Subgroup analysis indicated that CRP has a higher predictive value in infants with NEC who had a gestational age greater than 28 weeks and a birth weight exceeding 1500&#xa0;g.</p> Conclusion <p>CRP has significant clinical value in predicting the occurrence of NEC, disease progression, and the timing of surgical intervention.</p>