It has been found that aberrant expression of microRNAs (miRNAs) is strongly associated with carcinogenesis. In the present study, we investigated the expression of miR-155 and miR-146a in diffuse large B-cell lymphoma (DLBCL) patients (n=90). The expression levels of miR-155 and miR-146a were significantly higher in de novo DLBCL patients. miR-146a expression levels were associated with miR-155, lactate dehydrogenase, β 2 microglobulin, c-myc, International Prognostic Index status and Eastern Cooperative Oncology Group performance status. We found that patients with low miR-155 and miR-146a expression levels achieved a higher complete remission rate, higher overall response rate and longer progression-free survival time. Moreover, a high expression level of miR-155, but not miR-146a, was an independent indicator for chemotherapy protocol selection in our study. Patients with high expression of miR-155 received more survival benefits from rituximab treatment. These data suggest that miR-155 and miR-146a have potential as diagnostic and prognostic markers in DLBCL.