Quadruple negative breast cancer (QNBC), lacking the expression of ER (estrogen receptor), PR (progesterone receptor), HER2 (human epidermal growth factor receptor-2) and AR (androgen receptor), was regarded as one breast cancer subtype with the worst prognosis. Recently, the molecular features of QNBC are not well understood. Different from AR-positive triple-negative breast cancer, QNBC is insensitive to conventional chemotherapeutic agents and has no efficient treatment targets. However, QNBC has been shown to express unique proteins that may be amenable to use in the development of targeted therapies. Here we reviewed the features of QNBC and proteins that may serve as effective targets for QNBC treatment, such as ACSL4, SKP2, immune checkpoint inhibitors, EGFR, MicroRNA signatures and Engrailed 1.