It irreversibly inhibits 3 different ErbB family molecule members, including EGFR/human epidermal growth factor receptor (HER) 1, HER2, and HER4.[5] Dacomitinib-associated adverse events are often manifested by diarrhea, paronychia, dermatitis acneiform, interstitial lung disease, etc.[6,7] Severe intrahepatic cholestasis, caused by dacomitinib from simultaneously taking cytochrome P450 2D6 (CYP2D6) competitive substrates, has been rarely reported. Here, CYP2D6 is linked to intrahepatic cholestasis.