Objective To explore the correlation between nuclear magnetic resonance (MRI) perfusion parameters and collagen V (Type V collagen 2 chain, COL5A2), galectin-Galactoside lectin-3 (Galectin-3) and the diagnostic value of esophageal cancer. Method A total of 100 patients with suspected esophageal cancer admitted to our hospital from December 2020 to December 2021 were selected. With endoscopic and biopsy pathological examination as the gold standard, 55 patients with esophageal cancer were finally diagnosed as the observation group, and the other 45 patients with esophagitis lesions were the control group. All patients underwent magnetic resonance imaging and the levels of COL5A2 and Galectin-3 were determined. MRI perfusion parameters of the two groups were compared. The correlation between MRI perfusion parameters and tumor markers in patients with esophageal cancer was analyzed, and the diagnostic value of MRI perfusion parameters for esophageal cancer was analyzed. Results Compared to the benign group, levels of Ktrans, Kep and Ve were higher in the malignant group (P＜0.05). In contrast to patients with stage Ⅰ-Ⅱ oesophageal cancer, patients with Ktrans, Kep, and Ve levels were higher in stage Ⅲ and oesophageal cancer (P＜0.05). In contrast to patients with stage Ⅰ-Ⅱ oesophageal cancer, higher levels of COL5A2 and Galectin-3 in Ⅲ and stage esophageal cancer were higher (P＜0.05); Ktrans,Kep,Ve,COL5A2, and Galectin-3 in oesophageal cancer patients were all positively associated with disease stage (P＜0.05). Ktrans, Kep, and Ve were all positively correlated with COL5A2 and Galectin-3 levels (P＜0.05). In contrast to the single diagnosis of magnetic resonance imaging, COL5A2、Galectin-3, combined diagnosis had a high predictive value for oesophageal cancer (P＜0.05).Conclusion MRI perfusion parameters have some correlation with COL5A2 and Galectin-3 in esophageal cancer patients, and have certain diagnostic value for patients of different stages