Objectives: This study investigated the prognostic value of PIK3CA and TP53 during a 6-year follow-up of breast cancer patients. We also analyzed the impact of other factors on progression-free survival (PFS) and patients’ overall survival (OS). Methods: The expression of estrogen receptor (ER), progesterone receptor (PR), and Ki67 in cancer tissues was detected by immunohistochemistry. For each patient, Epidermal Growth Factor Receptor 2 (HER2 was evaluated using fluorescence in situ hybridization (FISH). Sanger sequencing was used to detect hotspot mutations in PIK3CA and TP53 genes. Results: Lymph node metastasis is the most important factor affecting the patient’s prognosis (74.3% vs. 81.6%, p = 0.04). The mutation rates of PIK3CA and TP53 in Triple-negative breast cancer (TNBC) patients were significantly higher than those of other breast cancer types (29.4% vs. 3.6%, p = 0.002). In TNBC, the PFS of patients with PIK3CA and TP53 mutations is poorer than non-carriers (0% vs. 75%, p = 0.003). The OS of breast cancer patients in Yunnan Province is lower than that of regions with rapid economic development in China (78.08% vs. 90.5%). Conclusions: Our results indicate that PIK3CA and TP53 mutations are poor prognostic factors for patients with TNBC. PIK3CA and TP53 mutations could be used as a predictor for prognosis in TNBC patients.