Spontaneous intracerebral hemorrhage (ICH) refers to non-traumatic vascular rupture and bleeding within the brain parenchyma. Its harm primarily stems from the space-occupying effect of the intracranial hematoma and secondary damage to the surrounding brain tissue. With the advancement of surgical techniques, the treatment of spontaneous ICH has shifted from traditional craniotomy to minimally invasive surgery (MIS), becoming one of the most promising technologies. MIS is fast, convenient, less traumatic, safe, effective, and cost-effective. One of the core aspects of this technique is the use of biochemical enzymes to liquefy the hematoma, allowing for safe and rapid removal of the hematoma and effectively improving patient outcomes. This article reviews the research progress on the treatment of ICH with MIS combined with hematoma liquefaction agents.