BACKGROUND: RNA N6-methyladenosine (m6A) regulators are essential for numerous biological processes and are implicated in various diseases. However, the comprehensive role of m6A regulators in the context of liver transplantation (LT) remains poorly understood. This study aimed to illustrate the relationship between m6A regulators and ischemia-reperfusion injury (IRI) following LT. METHODS: Datasets were acquired from the Gene Expression Omnibus database. Differential analysis of the merged data identified the differentially expressed m6A regulators. Random forest (RF) models and nomograms were used to forecast the incidence and assess the IRI risk following LT. m6A regulators were classified into distinct subgroups using cluster analysis. The differential gene expression was validated using immunohistochemistry, immunofluorescence, and Western blotting. RESULTS: We found significant disparities in the gene expression levels of the three m6A regulators between patients with and without LT. Wilms' tumor 1-associating protein (WTAP) expression was upregulated following LT. The RF models exhibited a high degree of accuracy in predicting IRI risk. Immune infiltration analysis showed that WTAP was an immune-associated m6A regulator that was closely associated with T and B cells. WTAP expression in the rat LT model was upregulated after 24 h of reperfusion, which was consistent with the results of the bioinformatics analysis. CONCLUSIONS: WTAP has a high diagnostic value for IRI in LT and influences the immune status of patients. Hence, WTAP, as a significant regulator of m6A, is a potential biomarker for the detection and implementation of immunotherapy for IRI following LT.