Diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin's lymphoma, displays marked heterogeneity. Although it is usually curable, 30-40% of patients die within 1-2 years due to refractory treatment or cancer relapse. In different types of cancer in humans, inorganic pyrophosphatase (PPA1) is deregulated, thereby contributing to tumorigenesis by supplying the tumor with an enormous energy source. However, the role of PPA1 in DLBCL is still unclear. Here, we analized PPA1 in 65 patients with DLBCL and 20 patients with reactive hyperplasia of the lymph nodes (control). The PPA1 level was significantly higher in patients with DLBCL than in control subjects (p < 0.05), and it is closely associated with B symptoms (i.e., fever, night sweats, and weight loss) and the IPI score (p < 0.05). Furthermore, PPA1 mRNA and protein levels were higher in most DLBCL cell lines than in the control HMy2.CIR cell line. Lastly, we investigated the effects of PPA1 knockdown on the proliferation and survival of the DLBCL cell line. We found that p53 and p21 expression decreased in PPA1-silenced DLBCL cells. In addition, cell proliferation decreased and cell apoptosis increased. In conclusion, PPA1 is a novel molecule that may be useful in the development and prognosis of DLBCL in the future.Keywords: Diffuse large B-cell lymphoma; Inorganic pyrophosphatase; Prognosis; Proliferation.