Nuclear factor‑κB (NF‑κB) is widely involved in various lymphoid malignancies. However, its exact functional role and potential regulatory mechanisms in Hodgkin's lymphoma (HL) remains unclear. The present study aimed to investigate the regulatory mechanism of NF‑κB in HL by analysis of a gene expression profile that was obtained from HL cells with or without NF‑κB subunit 2 (NFKB2) knockdown. The GSE64234 dataset containing 6 HL cell line specimens transfected with small interfering (si)RNA against NFKB2 and 6 control specimens transfected with non‑targeting siRNA sequences was downloaded from the Gene Expression Omnibus database. Based on these data, differentially expressed genes (DEGs) were screened for following data preprocessing. Functional enrichment analysis was subsequently conducted among the identified upregulated and downregulated DEGs. Additionally, a protein‑protein interaction (PPI) network was constructed and module analyses were performed. Finally, microRNAs (miRNAs/miRs) targeting the identified DEGs were predicted for the construction of a miRNA‑target regulatory network. A total of 253 DEGs were identified, consisting of 109 upregulated and 144 downregulated DEGs. Pathway enrichment analysis revealed that B‑cell lymphoma 2‑like 1 (BCL2L1) was significantly enriched in the NF‑κB signaling pathway, and colony‑stimulating factor 2 (CSF2) and BCL2L1 were enriched in the Jak‑signal transducer and activator of transcription (STAT) signaling pathway. BCL2L1 and CSF2 were determined to be hub genes in the PPI network. A total of 6 miRNAs, including let‑7a‑5p, miR‑9‑5p, miR‑155‑5p, miR‑135a‑5p, miR‑17‑5p and miR‑375, were identified in the miRNA‑target regulatory network. The results of the present study indicated that NFKB2 may be involved in HL development through regulation of BCL2L1, CSF2, miR‑135a‑5p, miR‑155‑5p and miR‑9‑5p expression, as well as the modulation of Jak‑STAT and NF‑κB signaling pathways.