In this study, we report that a short Fhit-derived peptide still able to physically bind ANXA4, recapitulates the Fhit wild-type activity with regard to ANXA4, as this Fhit sequence can prevent ANXA4 translocation to plasma membrane in paclitaxel-treated lung cancer cells, thus resulting in the restoration of chemosensibility to the drug both in vitro and in vivo experiments. Here, ANXA4 is linked to lung carcinoma.