LDHA activation induces tumor by activating tumor proliferation, growth, invasion, and metastasis. Whether LDHA mediated tumor metabolism that upon DLBCL occur remains unknown. Here, we investigated how LDHA adopt tumor metabolism after activation to regulate DLBCL-inducible. Here, we investigated LDHA is highly expressed in peripheral blood mononuclear cell (PBMC) of DLBCL patients. Knockdown of LDHA results in an increase in the apoptosis of cells, suppression of cell growth and migration in LY1 cells. We show that LDHA gains a canonical enzyme activity to produce lactate and triggers NAD+ in DLBCL cells. Furthermore, p-STAT5 was identified as a downstream target of LDHA, and p-STAT5 protein level was significantly reduced related to decreased LDHA protein expression. Collectively, our findings identify the oncogenic role of LDHA in DLBCL and suggest that LDHA can be considered as a pivotal prognostic biomarker and a potential therapeutic target.