Different to capsaicin, phenoxyethanol did not downregulate the expression of TRPV1 in HaCaT cells, suggesting that different regulatory mechanisms may exist for capsaicin and phenoxyethanol. Our experiments demonstrated that phenoxyethanol induces skin misperception and uncomfortable skin sensations like itching and burning comparable to capsaicin via activating TRPV1. The stimulation was inhibited by blocking TRPV1 with ID1609. The present data strengthened hitherto studies that TRPV1 plays a critical role in sensitive skin.