In summary, circHUWE1 downregulation inhibited DDP resistance, proliferation, migration, and invasion while it induced apoptosis and cell cycle arrest of DDP resistance-acquired NSCLC cells depending on the regulation of the miR-34a-5p/TNFAIP8 axis, supporting an important role of circHUWE1 in DDP-resistant NSCLC progression. The gene discussed is TNFAIP8; the disease is non-small cell lung carcinoma.