In short, activation of the ubiquitination system not only promotes the ubiquitin labelling of the EGFR‐EGF complex for proteasomal degradation but also targets the critical signalling pathways, such as the RAS–RAF–MEK signalling pathway, thereby inhibiting the biological behaviour of EGFR‐mutated or EGFR‐TKI‐resistant lung cancer cells through dual mechanisms. The gene discussed is EGF; the disease is lung cancer.