The molecular and clinical heterogeneity in diffuse large B‑cell lymphoma (DLBCL) has raised a need for the investigation of potential therapeutic biomarkers. MicroRNA‑320 (miR‑320) and CDK6 are both involved in the regulation of cell proliferation in various types of cancer. To investigate the clinical role of CDK6 in DLBCL, CDK6 expression was assessed using immunohistochemistry on formalin‑fixed, paraffin‑embedded sections. Furthermore, to investigate the relationship between CDK6 and miR‑320d, as well as their roles in cell proliferation, a series of experimentally functional validations was performed in DLBCL cell lines. Bioinformatics software and Dual‑Luciferase reporter assay were used to predict and validate the potential target of miR‑320d. In DLBCL cells transfected with miR‑320d lentiviral vector, CDK6 expression at the protein and mRNA levels was detected using western blotting and qRT‑PCR, respectively. Overexpression and small‑hairpin RNA knockdown of CDK6 were performed by lentiviral transduction. The results of these experiments revealed that CDK6 was overexpressed and predictive of poor prognosis in DLBCL patients. Moreover, CDK6 was revealed to be directly targeted by miR‑320d and either overexpression of miR‑320d or knockdown of CDK6 inhibited proliferation. In conclusion, CDK6 overexpression in DLBCL may result from miRNA‑320d downregulation and subsequent loss of inhibition of cell proliferation, suggesting that miRNA‑320d may be a potential therapeutic target for the treatment of DLBCL with high CDK6 expression.