In the current study, we explored the regulatory mechanism of HDAC inhibitor ITF2357 in the chemo-resistance of mut-KRAS NSCLC to Pem and found that HDAC inhibitor ITF2357 could reduce resistance of mut-KRAS NSCLC to Pem by regulating the miR-130a-3p/HDAC2/Rad51 axis. The gene discussed is HDAC9; the disease is non-small cell lung carcinoma.