MicroRNAs are short non‐coding RNAs that regulate gene expression. Previously, in a genome‐wide screen, we found deregulation of microRNA expression in psoriasis skin. MicroRNA‐21 (miR‐21) is one of the microRNAs significantly up‐regulated in psoriasis skin lesions. To identify the cell type responsible for the increased miR‐21 level, we compared expression of miR‐21 in epidermal cells and dermal T cells between psoriasis and healthy skin and found elevated levels of miR‐21 in psoriasis in both cell types. In cultured T cells, expression of miR‐21 increased markedly upon activation. To explore the function of miR‐21 in primary human T helper cells, we inhibited miR‐21 using a tiny seed‐targeting LNA‐anti‐miR. Specific inhibition of miR‐21 increased the apoptosis rate of activated T cells. Our results suggest that miR‐21 suppresses apoptosis in activated T cells, and thus, overexpression of miR‐21 may contribute to T cell–derived psoriatic skin inflammation.