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Chemoresistance is a major barrier against effective treatment outcomes in cancer.MDR cancer cells can survive through chemotherapy and give rise to a revisited tumor.The mechanisms of MDR involve multiple cellular events, such as overexpression of ATP-binding cassette transporters (typically, p-glycoproteins, P-gp) and malfunction of apoptosis.Cell-penetrating peptide-based strategies were developed for overcoming the barriers against effective cancer drug delivery, through the mechanisms including increased tumor penetration, enhanced intmcellular and intranuclear delivery, prolonged intracellular drug retention, thus yielding promising treatment benefits in the animal models.