Epithelial-mesenchymal transition (EMT) plays a critical role in embryonic development, wound healing, tissue regeneration, cancer progression and organ fibrosis. The proximal tubular epithelial cells undergo EMT, resulting in matrix-producing fibroblasts and thereby contribute to the pathogenesis of renal fibrosis. The profibrotic cytokine, TGF‑β, is now recognized as the main pathogenic driver that has been shown to induce EMT in tubular epithelial cells. Increasing evidence indicate that HIPK2 dysfunction may play a role in fibroblasts behavior, and therefore, HIPK2 may be considered as a novel potential target for anti-fibrosis therapy. Recently, members of the miR-200 family (miR‑200a, b and c and miR‑141) have been shown to inhibit EMT. However, the steps of the multifactorial renal fibrosis progression that these miRNAs regulate, particularly miR‑141, are unclear. To study the functional importance of miR‑141 in EMT, a well‑established in vitro EMT assay was used to demonstrate renal tubulointerstitial fibrosis; transforming growth factor‑β1‑induced EMT in HK-2 cells. Overexpression of miR‑141 in HK‑2 cells, either with or without TGF‑β1 treatment, hindered EMT by enhancing E‑cadherin and decreasing vimentin and fibroblast‑specific protein 1 expression. miR‑141 expression was repressed during EMT in a dose‑ and time‑dependent manner through upregulation of HIPK2 expression. Ectopic expression of HIPK2 promoted EMT by decreasing E-cadherin. Furthermore, co-transfection of miR‑141 with the HIPK2 ORF clone partially inhibited EMT by restoring E‑cadherin expression. miR‑141 downregulated the expression of HIPK2 via direct interaction with the 3'-untranslated region of HIPK2. Taken together, these findings aid in the understanding of the role and mechanism of miR‑141 in regulating renal fibrosis via the TGF‑β1/miR-141/HIPK2/EMT axis, and miR-141 may represent novel biomarkers and therapeutic targets in the treatment of renal fibrosis.