Glioblastoma, the most common tumor in the brain, has witnessed very little clinical progress over the last decades. Exploring and discovering new therapeutic strategies for glioblastoma has become a critical problem. Harmine (HM), belonging to the beta-carboline alkaloid, is a natural product and isolated from the seeds of Peganum harmala L., which own notable antitumor activity in vitro . However, the poor water solubility and less selectivity of HM severely limit its clinical use. For enhancing its selective ability to tumor cells, we fabricated a kind of protein nanoparticles (BSA-HM NPs), composed of the modified bovine serum albumin (BSA) and HM. It was substantiated through in vitro and in vivo experiment that BSA-HM NPs could predominantly accumulate in tumor tissues and exhibited remarkably enhanced antitumor efficacy. This study provides a promising strategy to improve the bioavailability and avoid side effects of HM as antitumor agents by choosing BSA as carriers.