Simple Summary Palbociclib is one of the preferred treatments for hormone-receptor-positive, HER2-negative metastatic breast cancer in women; its effectiveness and safety in the Chinese real-world population require further investigation. Our study aimed to identify the clinical outcomes of patients who received palbociclib in combination with endocrine therapy (ET) in China. The effectiveness of palbociclib plus ET in treating metastatic breast cancer was confirmed in 397 Chinese patients across eight clinical sites. The regimens were well tolerated by both the general and elderly groups. However, some factors were identified as potential hindrances to the therapy's benefits, including higher Ki-67 expression, primary resistance to ETs, liver metastases, more metastatic sites, later line of therapy, and the use of fulvestrant instead of aromatase inhibitors. Palbociclib is useful for treatment of metastasis breast cancer, and our study may provide a basis for further research.Abstract Background: Palbociclib has been approved for marketing in China. However, its effectiveness, safety, and latent variables in the Chinese population require further investigation. Methods: Information was retrieved from 397 patients with metastatic breast cancer (mBC) who received at least two cycles of palbociclib plus endocrine therapy (PAL plus ET) at eight clinical sites in China. The patients' demographic characteristics, treatment patterns, and adverse events (AEs) were analyzed. Results: The objective response rate (ORR) and clinical benefit rate (CBR) for PAL plus ET were 28.97% and 66.25%, respectively. The median PFS was 14.2 months in the whole population. In addition to protein Ki-67 status and sensitivity to ETs, no liver metastases, fewer metastatic sites, an earlier line of therapy, and treatment combined with AI instead of FUL were also considered as independent prognostic factors for PAL treatment. Administration of PAL was generally well tolerated in patients with hormone-receptor-positive and human-epidermal-growth-factor-receptor-2-negative (HR+/HER2-) advanced breast cancer (ABC). The therapy was safe in the elderly population, which is consistent with the outcomes of the whole population and previous reports. Conclusions: In this most widely distributed study in China to date, palbociclib combined with ET proved its effectiveness for HR+/HER2- ABC treatment, and adverse events were manageable. Here, we identified some independent prognosis factors, but the mechanism by which these factors influence effectiveness requires further verification.