Objective To investigate the efficacy and safety of superselective arterial thrombolysis combined with mechanical thrombectomy for the treatment of acute cerebral infarction. Methods Thirty patients with acute cerebral infarction were treated with superselective arterial thrombolysis combined with mechanical thrombectomy. The vascular recanalization was illustrated by digital subtraction angiography (DSA). The neurological deficits were assessed by NIHSS before thrombolysis and 7 d, 1 month and 3 months after thrombolysis. The state of consciousness was evaluated by GCS before thrombolysis, immediately after thrombolysis and 1 d and 3 d after thrombolysis. The state of life was examined by Barthel Index (BI) 1 month and 3 months after thrombolysis. The symptomatic intracranial hemorrhage after thrombolysis was investigated by brain CT scan. Results After treatment, 26 patients had vascular recanalization, and the rate of vascular recanalization was 86.7%. The scores of NIHSS 7 d, 1 month and 3 months after thrombolysis were significantly lower than that before thrombolysis (P<0.05). The GCS scores immediately after thrombolysis and 1 d and 3 d after thrombolysis were significantly higher than that before thrombolysis (P<0.05). The good rates of BI were 76.7% and 80.0% respectively 1 month and 3 months after thrombolysis. The imaging examination revealed that the prevalence of symptomatic intracranial hemorrhage rate was 6.7%. Conclusion Superselective arterial thrombolysis combined with mechanical thrombectomy in treatment of acute cerebral infarction can improve the rate of recanalization and prognosis of patients, which is a relatively safe and effective method.