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Potassium ions (K + ) released from dying necrotic tumour cells accumulate in the tumour microenvironment (TME) and increase the local K + concentration to 50 mM (high-[K + ] e ). Here, we demonstrate that high-[K + ] e decreases expression of the T-cell receptor subunits CD3ε and CD3ζ and co-stimulatory receptor CD28 and thereby dysregulates intracellular signal transduction cascades. High-[K + ] e also alters the metabolic profiles of T-cells, limiting the metabolism of glucose and glutamine, consistent with functional exhaustion. These changes skew T-cell differentiation, favouring Th2 and iT reg subsets that promote tumour growth while restricting antitumour Th1 and Th17 subsets. Similar phenotypes were noted in T-cells present within the necrosis-prone core versus the outer zones of hepatocellular carcinoma (HCC)/colorectal carcinoma (CRC) tumours as analysed by GeoMx digital spatial profiling and flow-cytometry. Our results thus expand the understanding of the contribution of high-[K + ] e to the immunosuppressive milieu in the TME., (© 2024 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.)