Background: The most frequent lymphoma in Egyptian adults is diffuse large B-cell lymphoma (DLBCL). Patients with DLBCL experienced a wide variety of prognoses. It has become challenging to identify high-risk groups using IPI alone because the outcome of DLBCL patients has improved with the introduction of rituximab. It would thus be important to find prognostic indicators for predicting patient subgroups with poor prognosis and choose the efficient therapy regimen in accordance. One of the factors thought to contribute to the formation of cancer metastases and cancer progression is inflammation. The systemic immune inflammation index (SII) is a reliable indicator of cancer patients' prognosis. It seems that nutritional status affects how different solid tumors behave. To evaluate the immunological nutritional condition of cancer patients, the Prognostic Nutritional Index (PNI) was developed. The goal of our research was to assess SII and PNI's prognostic and predictive significance in DLBCL patients receiving RCHOP therapy. Method: This prospective, non-randomized study aimed to evaluate the prognostic value of SII and PNI in patients DLBCL receiving RCHOP. Eightyfour patients were included. Results: The optimal cut-off values for PNI and SII using the ROC curve were 50 and 410, respectively. PNI and SII were significantly associated with a complete remission rate. Multivariate analyses showed that low PNI and high SII were independent predictors of poor relapse-free and overall survival. Conclusions: A growing body of evidence demonstrates the value of pretreatment PNI and SII as simple prognostic indicators in DLBCL patients receiving RCHOP.