Objective To explore the changes of serum C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) levels in patients with non-Hodgkin's lymphoma (NHL) and their relationship with prognosis. Methods A total of 93 patients with NHL in the hospital were enrolled as study group between January 2019 and June 2020. According to survival situations within 1 year, they were divided into survival group (n=74) and death group (n=19). And other 50 healthy controls during the same period were enrolled as control group. The levels of serum CRP, PCT and IL-6 were detected and compared among all groups. The above three indexes in NHL patients with different pathological characteristics were analyzed. The relationship between serum CRP, PCT, IL-6 levels and prognosis of NHL patients was analyzed by receiver operating characteristic (ROC) curves. Results The levels of serum CRP, PCT and IL-6 in study group were higher than those in control group (P＜0.05). The levels of serum CRP, PCT and IL-6 were related to Ann Arbor staging, pathological types, tumor size and differentiation degree (P＜0.05). The levels of serum CRP, PCT and IL-6 in death group were higher than those in survival group (P＜0.05). ROC curves analysis showed that AUC of serum CRP combined with PCT and IL-6 for assessing prognosis of NHL patients was 0.910,greater than that of them alone (0.739, 0.702, 0.720) (P＜0.05). Conclusion The levels of serum CRP, PCT and IL-6 are higher in NHL patients, which are affected by Ann Arbor staging, pathological types, tumor size and differentiation degree. The three are expected to be the indexes to assess the prognosis of NHL.