To evaluate the feasibility and safety of minimally invasive intracranial hematoma suction drainage surgery (MIS) plus intraclot use of recombinant tissue-type plasminogen activator (rt-PA) in patients with spontaneous intracerebral hemorrhage (ICH) and to explore the potential treatment regimen of intraclot rt-PA. Methods: Patients with ICH treated with MIS and intraclot rt-PA were retrospectively identified. A volumetric analysis to assess hematoma and perihematomal edema (PHE) volumes was conducted. Glasgow Coma Score (GCS) was used to assess consciousness. The modified Rankin Scale (mRS) was used for scoring clinical outcomes (mRS 0~3 v.s. 4~5). The observed 30-day cohort mortality was compared with its predicted mortality. Results: Forty-five patients were included. The median number of doses and dose of rt-PA was 2 (1) doses and 1.5 (1) mg, with a maximum cumulative dose of 4.0 mg. The ICH volume and PHE volume post-MIS was significantly lower compared with that of pre-MIS, respectively (P=0.000; P=0.000). There was a significantly negative correlation between puncture accuracy and residual hematoma volume (ρ = －0.61; P < 0.01). GCS at post-MIS was significantly higher than that at pre-MIS (P=0.000). The 30-day patient morality was 0, significantly lower than the predicted mortality (46.7%). No patients developed intracranial infection, and only 2 patients experienced rebleeding. The patients were followed up for a median of 2.5 years; 5 patients died, 3 patients lost contact, and 21 patients had good outcomes (mRS 0~3). Conclusion: MIS combined with low dose rt-PA in the treatment of ICH enhances clot evacuation, lowers 30-day mortality, and improves long-term clinical outcome. The rt-PA dosage regimen of 0.5～1.0 mg/12～24 h, ≤4.0 mg cumulative may be favorable for treatment in ICH patients receiving minimally invasive surgery