Recent studies have demonstrated the role of caspase-14 in terminally differentiated keratinocytes, and its expression may decrease the magnitude of tumors in the epidermis. In the present study, we assessed the potential of luteolin (LUT) to elicit the expression of caspase-14 in terminal differentiation of human keratinocytes. The semi-qualitative RT-PCR data revealed a significant level of caspase-14 expression in LUT-treated human immortalized keratinocytes (HaCaT) with respect to untreated cells. The quantitative data (ELISA) further supported the potency of LUT to induce caspase-14 expression at 3.19 ng/ml when compared to 1.29 ng/ml of vitamin D3 (positive control). Further, the enhanced expression of human involucrin gene in LUT-treated HaCaT cells confirmed its ability to drive terminal differentiation in these cells. These preliminary results provide first-hand information about the in vitro potential of LUT to elicit the expression of caspase-14, thereby inducing terminal differentiation in human keratinocytes. © 2015, The Society for In Vitro Biology.