microRNA‑21 (miRNA/miR‑21) is a well‑known oncogenic miRNA that is overexpressed in various carcinomas. The tumor suppressor genes, programmed cell death 4 (PDCD4) and phosphatase tensin homologue (PTEN), which target miR‑21, are underexpressed in several types of cancer. However, the expression of miR‑21 and its target genes, PDCD4 and PTEN, has not yet been reported in skin squamous cell carcinoma (SCC). In the present study, anti‑miR‑21 was transfected into the A431 cell line, and the expression of miR‑21, PDCD4 and PTEN and the level of cell apoptosis were detected by quantitative polymerase chain reaction, immunocytochemistry and western blotting, and terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling, respectively. The expression levels of PDCD4 and PTEN in the A431 cell line transfected with anti‑miR‑21 were significantly increased (P< 0.05) and the apoptotic ratio was significantly increased (P< 0.05). The data indicate that miR‑21 may play an oncogenic role in the cellular processes of SCC and represent a novel target for effective therapies.