Background The International Prognostic Index and its modifications are used to estimate prognosis in non-Hodgkin lymphoma. However, the outcome is often different in patients with similar index scores. Aim The aim of this study was to elaborate a prognostic model for patients with mature B-cell non-Hodgkin lymphoma using a combination of predictive markers. Material and methods The study included 45 patients with mature B-cell non-Hodgkin lymphoma. Before the administration of treatment, clinical and laboratory parameters were measured. After the 35-month follow-up period, overall survival was studied in relation to the data obtained at initial examination. Results We revealed nine adverse predictive markers for overall survival of enrolled patients: Eastern Cooperative Oncology Group (ECOG) performance status >1; erythrocyte sedimentation rate >30 mm/h; levels of hemoglobin <120 g/L, fibrinogen ≥6 g/L, interleukin-6 ≥2 pg/mL, tumor necrosis factor ≥1.45 pg/mL, soluble fibrin monomer complexes >4 mg/dL, high-density lipoprotein cholesterol <1.03 mmol/L in men, and <1.29 mmol/L in women; and short activated partial thromboplastin time. A prognostic model for the estimation of the risk of death within the ensuing 1.5–2 years in patients with non-Hodgkin lymphoma was constructed. Conclusion Markers of inflammation, anemia, hypercoagulability, dyslipidemia, and poor ECOG status are associated with worse survival in patients with mature B-cell non-Hodgkin lymphoma.