Microtubules, highly dynamic components of the cytoskeleton, are involved in mitosis, cell migration and intracellular trafficking. Our previous work has shown that the centrosomal protein Cep70 regulates microtubule organization and mitotic spindle orientation in mammalian cells. However, it remains elusive whether Cep70 is implicated in microtubule stability. Here we demonstrate that Cep70 enhances microtubule resistance to cold or nocodazole treatment. Our data further show that Cep70 promotes microtubule stability by regulating tubulin acetylation, and plays an important role in stabilizing microtubules. Mechanistic studies reveal that Cep70 interacts and colocalizes with histone deacetylase 6 (HDAC6) in the cytoplasm. These findings suggest that Cep70 promotes microtubule stability by interaction with HDAC6 and regulation of tubulin acetylation.