Objective To explore the relationship between the expression levels of chemokine 9 (CXCL9) and its receptor CXCR3 in the tissues of patients with diffuse large B-cell lymphoma (DLBCL) and clinicopathological characteristics and prognosis. Methods From January 2015 to January 2016, 92 patients with DLBCL treated with R-CHOP chemotherapy in our hospital were collected, and DLBCL tumor tissue samples and 50 normal lymph tissue samples near the focus were obtained through lymph node biopsy. The expression of CXCL9 and CXCR3 genes in DLBCL tumor tissues and normal lymphoid tissues was analyzed by cancer genome atlas (TCGA) database, and the positive expression of CXCL9 and CXCR3 protein in DLBCL tumor tissue and normal lymphoid tissue was analyzed by immunohistochemistry, and the relationship between CXCL9 and CXCR3 protein expression levels and clinicopathological characteristics and prognosis was analyzed. Kaplan Meier method was used to analyze the relationship between the expression levels of CXCL9 and CXCR3 protein and the recurrence of DLBCL. COX regression was used to analyze the risk factors of recurrence in patients with DLBCL. Results The expression levels of CXCL9 and CXCR3 genes in DLBCL tumor tissues in the TCGA database were significantly different from those in normal lymphoid tissues (P＜0.05); the positive expression rates of CXCL9 and CXCR3 proteins in DLBCL tumor tissues were significantly higher than their positive expression rates in normal tissues (P＜0.05); there was a positive correlation between CXCL9 and CXCR3 proteins expression in DLBCL tumor tissue (x2=15.836, P＜0.001); the expression levels of CXCL9 and CXCR3 protein were not related to the age, gender, primary site, lactate dehydrogenase level, and international prognostic index (IPI) score of DLBCL patients (P＞0.05), but were related to Ann Arbor stage, histological type and Ki67 positive rate (P＜0.05); the 5-year cumulative recurrence rate of DLBCL patients in CXCL9 high expression group was 68.52%, which was significantly higher than 37.50% of patients in low expression group, and the difference was statistically significant (x2=9.788, P＜0.001); the 5year cumulative recurrence rate of CXCR3 high expression group was 73.68%, which was significantly higher than 28.57% of low expression group, and the difference was statistically significant (x2=17.610, P＜0.001); the results of multivariate COX analysis showed that high expression of CXCL9, high expression of CXCR3, Ann Arbor stages Ⅲ to Ⅳ and non germinal center were independent risk factors for recurrence in DLBCL patients (all P＜0.05). Conclusion The expressions of CXCL9 and CXCR3 in tumor tissues of DLBCL patients are upregulated, and their expression levels are related to the Ann Arbor stage and histological type of patients, which may be potential targets indicating the prognosis of DLBCL patients.