CDK4/6 inhibitors are applied for the treatment of breast cancer. The purpose of this study was to explore the effects of palbociclib (PALB) on triple-negative breast cancer. An in vivo assay was applied to determine the effects of PALB on breast cancer. Gene expression was detected using immunohistochemistry. mRNA levels were detected using reverse transcription-quantitative PCR. Protein expression was detected using western blot. The expansion of CD8+ T cell subsets was detected using flow cytometry. We found that PALB treatment promoted the persistence of CD8+ T cells, manifested by the maintenance of stem-like CD8+ T cells and effector T cells. Moreover, PALB downregulated PHGDH, high levels of which predicted poor prognosis of breast cancer patients. Moreover, overexpression of PHGDH antagonized the effects of PALB and suppressed the persistence of CD8+ T cells. Additionally, PALB enhanced the effects of anti-PD1 immunotherapy and suppressed the tumor growth of breast cancer. In summary, PALB promoted the maintenance of CD8+ memory precursors in breast cancer via downregulating PHGDH.