In the present study, to elucidate the mechanisms of TBX6‐induced CS at the protein level, we employed a comparative proteomics strategy of iTRAQ to explore the differential protein expression profiles, GO terms, IPA network and pathway and hierarchical clustering between normal control and CS patients with both TBX6 deletion and T‐C‐A haplotype. The gene discussed is TBX6; the disease is Cowden syndrome 1.