Abstract: ob＜x＞jective To investigate the effect of serum ferritin and related clinical features on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). Methods The general data, laboratory and imaging examinations, and immunohistochemical staining results of 202 newly diagnosed DLBCL patients with exact serum ferritin values were collected from 7 medical centers from March 2015 to November 2020. The optimal truncation values of ferritin, age and albumin were calculated by MaxStat statistics. Univariable and multivariable analyses were performed using the Cox proportional risk model to determine the variables affecting the survival outcome of patients with DLBCL and subgroup analysis was performed. Results Among the 202 newly diagnosed DLBCL patients, 105 (51.9%) were males and 97 (48.1%) were females. The median age was 58 years old, 74 (36.6%) were Ann Arbor I/Ⅱ stage. The median follow-up time was 36 months. The results of Mann-Whitney U test showed that there were statistically significant differences in serum ferritin, age and albumin between the survival group and the death group (P < 0.05). The optimal cut-off values of serum ferritin, age and albumin were 246ng/ mL, 74 years and 38.5g/L, respectively. Univariate and multivariate analysis showed that ferritin, age and ECOG score had influence on the prognosis of DLBCL. In the low-risk and low-medium-risk IPI groups, the OS difference of patients with FER < 246ng/ml and FER ≥246ng/ml was significant (P < 0.05), but no significant difference was found in the Bcl-2+, Bcl-6- group, IPI high-risk group and IPI high-risk group. Conclusion Serum ferritin is a poor prognostic factor in patients with DLBCL and helps to distinguish poor prognostic patients with low risk of IPI.