Although follicular lymphoma (FL) is a pathological entity characterized by relatively uniform histological and molecular findings, its clinical course is highly variable. Establishment of therapeutic strategies based on a simple and practical prognostic model is important. C-reactive protein (CRP) is an adverse prognostic marker for various tumors and aggressive lymphomas. However, the significance of serum CRP levels as a prognostic index in low-grade lymphomas, such as FL, has not been thoroughly investigated. We retrospectively analyzed the relationship between serum CRP levels at diagnosis and the prognosis in patients with FL ( n  = 61) undergoing rituximab-containing chemotherapy. Elevated CRP levels showed a significant association with elevated fibrinogen ( P  = 0.002) in univariate analysis. Patients with higher CRP levels (> 5 mg/L) had a significantly shorter progression-free survival in multivariate analysis ( P  = 0.044). We concluded that serum CRP levels are important in prognostic stratification of patients with FL.