Objective · To detect the expressions of proto-oncogene protein FOSB and cyclin protein P16 in the different molecular subtypes of breast invasive ductal cancer and their correlation. Methods · The tumor tissues of 138 patients diagnosed with breast invasive ductal cancer by postoperative pathological examinations in Zhongshan Bo'ai Hospital from August 2013 to March 2019 were collected with normal breast tissues as control. Immunohistochemical staining was performed for the expressions of FOSB and P16 to investigate their correlation in the breast cancer. Besides, their expressions and their correlations in the different molecular subtypes of breast cancers, i.e. Luminal A, Luminal B [According to the expression of human epidermal growth factor 2 (HER2), it can be divided into HER2- and HER2+.], HER2 positive subtype, and triple-negative breast cancer (TNBC), were also detected. Results · ① The expression level of FOSB in 138 cases of breast invasive ductal cancer tissues was negatively correlated with P16 (r=-0.181, P=0.033). ② The expression of FOSB was significantly higher in Luminal A than those in other subtypes (P=0.028, P=0.033, P=0.001, P=0.010), while the expression of P16 was significantly higher in TBNC than those in other subtypes (P=0.025, P=0.005, P=0.008, P=0.011). ③ The expression level of FOSB in TBNC was negatively correlated with the expression of P16 (r=-0.566, P=0.018). Conclusion · The expressions of FOSB and P16 in the different molecular subtypes of breast invasive ductal cancer are different. The expression level of FOSB significantly increases in Luminal A, and that of P16 significantly increases in TBNC. There is a negative correlation between the expression levels of FOSB and P16 in TBNC.