The NAD‐dependent protein deacetylase Sir2 (silent information regulator 2) regulates cellular lifespan in several organisms. Histone deacetylase 4 (HDAC4) belongs to the class IIa group of histone deacetylases; this class of HDACs is composed of proteins that are important regulators of gene expression that control pleiotropic cellular functions. However, the role of HDAC4 in cellular senescence is still unknown. Here, we show that the expression patterns of HDAC4 and SIRT1 (Sirtuin 1, the mammalian homolog of Sir2) are positively correlated during cellular senescence. Moreover, the overexpression of HDAC4 delays senescence, whereas the knockdown of HDAC4 leads to premature senescence in human fibroblasts. Furthermore, we demonstrate that HDAC4 increases endogenous SIRT1 expression by enhancing its sumoylation modification levels, thereby stabilizing its protein levels. Therefore, our study provides a new molecular mechanism for the regulation of cellular senescence. This article is protected by copyright. All rights reserved.