Breast cancer, the most common cancer in women, is a serious public health issue. Triple-negative breast cancer (TNBC), which lacks expression of the estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2, accounts for ∼15% of breast cancer cases. Treatment of TNBC patients has proven difficult because of the lack of expression of hormone receptors. We conducted a retrospective study to investigate the prognostic impact of histone methyltransferase, hSETD1A, on overall survival in TNBC cases after surgery. In total, 159 TNBC cases were enrolled and clinicopathological characteristics were obtained from medical records. hSETD1A status of each subject was determined using immunohistochemistry. The chi-squared test was used to compare 5-year overall survival rates of all subjects according to clinical characteristics, and both univariate and multivariate analyses were conducted to calculate the hazard ratios and 95% confidence intervals. Advanced tumor-node-metastasis stage stage, larger tumor size, vascular invasion, metastasis in the initial diagnosis, and hSETD1A expression were correlated with worse outcome. Among all factors identified, metastasis in the initial diagnosis had the greatest impact on survival. The results indicated that hSETD1A positivity was correlated with shorter survival among TNBC cases, suggesting it may serve as a prognostic biomarker for patients with TNBC.