Aldosterone has been shown to mediate p21‐dependent cellular senescence in rat kidney proximal tubules in vivo and in cultured human proximal tubular cells. p21‐induced senescent cells expressed higher levels of apoptotic cytokines, such as tumour necrosis factor‐α (TNF‐α), compared to non‐senescent cells. The aim of this study was to investigate the hypothesis that aldosterone increases proximal tubular apoptosis by increasing the secretion of apoptosis‐inducing factors through a p21‐dependent mechanism. Human proximal tubular cells were incubated with aldosterone (10 nmol/L) and cell senescence was detected by senescence‐associated β‐galactosidase staining and expression of p21. Apoptosis was analysed by terminal nick‐end labelling and annexin/propidium iodide staining. p21 localisation was observed by immunofluorescence. Aldosterone for 3 or 5 days increased senescence‐associated β‐galactosidase staining, expression of p21 and TNF‐α mRNAs, and secretion of TNF‐α into the culture medium. These changes were abolished by gene silencing of p21. Aldosterone failed to increase apoptotic cells at day 3, but did increase them at day 5. Neutralising antibody against TNF‐α prevented the aldosterone‐induced apoptotic changes. Aldosterone did not affect the localisation of p21. These findings indicate that aldosterone increases TNF‐α synthesis and secretion in proximal tubular cells via p21/senescence‐dependent cell phenotypic changes, and that secreted TNF‐α plays an important role as a paracrine factor in mediating cell apoptosis, indicating a possible involvement in aldosterone‐induced renal damage. © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Wiley Publishing Asia Pty Ltd