As an important substrate for cell metabolism, the short-chain fatty acid acetate emerges as a regulator of cell fate and function. However, its role in T-cell survival and its underlying mechanisms remain largely unknown. Here, we demonstrate that acetate modulates T-cell apoptosis via potentiation of α-tubulin acetylation. We further show that acetate treatment effectively increases the expression of the tumor necrosis factor receptor (TNFR) family member CD30 by enhancing its gene transcription. Moreover, CD30 physically associates with and stabilizes the deacetylase HDAC6, which deacetylates α-tubulin to decrease microtubule stability. Proteomic profiling of CD30 knockout (Cd30-/-) T-cells reveals elevated expression of anti-apoptotic BCL2 family proteins and thus promotes T-cell survival via a microtubule-Bcl-2 axis. Taken together, our results demonstrate that acetate is a regulator of T-cell survival by controlling levels of acetylated α-tubulin. This suggests that therapeutic manipulation of acetate metabolism may facilitate optimal T-cell responses in pathological conditions.