In this work, we discovered that a higher exosomal miR‐3126‐5p level in peripheral blood plasma suggested a poor prognosis of NSCLC patients, and CAFs‐derived exosomal miR‐3126‐5p targeted KLF13 and consequently activated the SH2B1/IRS1 axis to promote PI3K/AKT pathway‐mediated glycolysis, thus accelerating the progression of NSCLC. Here, SH2B1 is linked to non-small cell lung carcinoma.