Simultaneously, GSEA based on the sequencing results indicated that the NF-κB and HIF1α pathways were most related to the differential expression of COMMD3. Therefore, our in vitro and in vivo analyses indicated the activating effect of COMMD3 on the HIF1α/VEGF/NF-κB pathway leading to the promotion of the angiogenesis and progression of HCC. The gene discussed is NFKB1; the disease is hepatocellular carcinoma.