The feedback loops have been reported in many cancers, such as the positive feedback loop between miR‐181b and STAT3 in colon cancer,41 the negative feedback loop between miR‐200a and HDAC4 in hepatocellular carcinoma.42 Feedback loops could amplify the effects of interaction molecules in caners and more significantly promote the aberrant expression of these molecules.43 In this study, we further found that targeting the feedback loop between EGR4 and ZNF205‐AS1 via concurrently depleting EGR4 and ZNF205‐AS1 significantly repressed NSCLC tumour growth in vivo. The gene discussed is HDAC4; the disease is malignant colon neoplasm.