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Background: Epigenetic regulation plays vital roles in the oncogenesis and treatment of diffuse large B-cell lymphoma (DLBCL). The H3K9me3-specific histone methyltransferase SUV39H1 is an epigenetic gene that promotes the progression of a variety of malignancies. However, the roles of SUV39H1 in DLBCL remain unclear.Methods: Initially, the Oncomine, Cancer Cell Line Encyclopedia (CCLE), UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) databases were searched to explore the expression of SUV39H1 in DLBCL. The clinical parameters and pathological sections of 61 successive patients, including 47 cases of DLBCL and 14 cases of reactive lymphoid hyperplasia, were collected from January 2019 to November 2020. Immunohistochemistry was conducted to verify the results of the database search. Finally, relevant parameters and pathological results were combined to analyze the expression of SUV39H1.Results: We found that the expression of SUV39H1 in DLBCL tissues was higher than that in normal and other cancer tissues (PP=0.037), suggesting that patients with high SUV39H1 expression are less likely to develop tumors over 7.5 cm in size. Regarding survival, the group with high SUV39H1 expression had a lower survival rate than the group with low SUV39H1 expression in terms of 10-year disease-free survival (DFS) according to the database analyses (P=0.035). However, SUV39H1 was revealed as an independent predictor of overall survival (OS) and progression-free survival (PFS) in patients from both databases and our hospital (P>0.05).Conclusion: SUV39H1 expression is higher in DLBCL tissues than in normal and other cancer tissues, indicating that DLBCL patients may not develop bulky tumors over follow-up and suggesting that SUV39H1 might serve not only as a predictive factor in the clinic but also as a target for the epigenetic therapy of DLBCL.