To investigate the clinical significance of serum LRG1, LDH and β2-MG in the recurrence of diffuse large B-cell lymphoma(DLBCL) after chemotherapy.The serum levels of LRG1, LDH and β2-MG of 80 patients with DLBCL were detected before treatment and followed up for these patients was performed. The cut-off value of non-recurrent survival was determined by ROC analysis. The correlation of three serum markers for predicting recurrence with prognostic factors of diffuse large B-cell lymphoma patients after treatment was analyzed by ROC curve.The serum levels of LDH, LRG1 and β2-MG were higher in the groups with high tumor stageing, extranodal invasion and bone marrow involvement, respectively(P＜0.05). The optimal cut-off values for predicting recurrence risk determined by ROC analysis: LDH 402.37 U/L, LRG1 1.81 mg/L and β2-MG 168.3 ng/L, respectively.COX multivariate regression analysis showed that serum LRG1 was an independent factor affecting the recurrence of diffuse large B-cell lymphoma(P＜0.05).The serum level of LRG1 may become a new biological marker to predict the recurrence risk of diffuse large B-cell lymphoma.