Background: In the real world, there are still a large number of HR+/HER2- advanced breast cancer patients receiving initial endocrine therapy with fulvestrant monotherapy in China, especially patients with bone metastases only. It is due to lack of data comparing the effective between Palbociclib combined with AI and fulvestrant monotherapy as initial endocrine therapy. On the other hand, there are economic factors and access issues. According to the National Cancer Center's previous clinical experience, Palbociclib combined with AI is superior to fulvestrant monotherapy in HR+/HER2- advanced breast cancer patients receiving initial endocrine therapy. Therefore, we collected and summarized the previous clinical data in our center to compare the effective of Palbociclib combined with AI and fulvestrant monotherapy for HR+/ HER2-advanced breast cancer patients receiving initial endocrine therapy in China. Methods: This is a retrospective real-world experience aimed at verifying the effective of Palbociclib combined with AI and fulvestrant monotherapy for HR+/ HER2-advanced breast cancer patients receiving initial endocrine therapy in China. The primary aim was rwPFS; secondary aims were overall survival, and objective response rate. Patients received Palbociclib combined with AI or fulvsetrant monotherapy. Results: In total, 346 patients were enrolled, 193 to Palbociclib plus AI and 153 to fulvestrant monotherapy. Median age was 55 years (range 28-88); 191 had visceral involvement (116 in Palbociclib plus AI group and 75 in fulvestrant group). At a median follow up of 38 months (range 4-78). The median PFS was 20.0 months (95% CI 17.3–22.7) in the Palbociclib plus AI group and 12 months (95% CI 9.6–14.3) in the fulvestrant group (hazard ratio 0.593, 95% CI 0.470–0.749, p<0·0001). The 6-month progression-free rate was 83.9% in the Palbociclib plus AI group and 75.8% in fulvestrant group. The 6-month progression-free rate was 83.9% in the Palbociclib plus AI group and 75.8% in fulvestrant group. The 12-month progression-free rate was 65.8% in the Palbociclib plus AI group and 46.4% in fulvestrant monotherapy group. The over survival was not reached in the Palbociclib plus AI group and it was 65 months (95% CI 55.6–75.4) in the fulvestrant group. Grade 3-4 adverse events occurred in Palbociclib plus AI group. The most common grade 3 or 4 adverse events were neutropenia (47.7%) and leucopenia (27.5%) in the Palbociclib plus AI group. Conclusions: The efficacy of palbociclib plus AI is worthy of recognition and the toxicity was acceptable. Compared with fulvestrant monotherapy in HR+/HER2- advanced breast cancer patients receiving initial endocrine therapy, Palbociclib plus AI might have a better survival. Clinical trial information: NCT05000736.