Inclusion Criteria:  Age ≥18 years; Acute ischemic stroke symptom onset between 4.5 to 24 hours prior to enrollment; including wake-up stroke and unwitnessed stroke, onset time refers to 'last normal time'; Pre-stroke mRS score≤1; Baseline NIHSS 6-25 ( both included ); Neuroimaging: Internal carotid artery, middle cerebral artery M1 or M2 occlusion confirmed by CTA/MRA ( carotid artery occlusion refers to carotid artery or intracranial artery, with or without tandem occlusion ), and target mismatch profile on CT perfusion ( CTP ) or MRI_perfusion weighted imaging ( MRI_PWI ) including ischemic core volume <70 mL, mismatch ratio≥1.8 and mismatch volume≥15 mL demonstrated by a certified automatic software; written informed consent from patients or their legally authorized representatives.  Exclusion Criteria:  Intended to proceed to endovascular treatment; Allergy to rhTNK-tPA; Rapidly improving symptoms at the discretion of the investigator; NIHSS consciousness score 1a >2, or epileptic seizure, hemiplegia after seizures ( Todd's palsy ) or combined with other nervous/mental illness not able to cooperate or unwilling to cooperate; Persistent blood pressure elevation ( systolic ≥180 mmHg or diastolic ≥100 mmHg ), despite blood pressure lowering treatment; Blood glucose <2.8 or >22.2 mmol/L ( on random glucose testing is acceptable ); Active internal bleeding or at high risk of bleeding, e.g.: Major surgery, trauma or gastrointestinal or urinary tract haemorrhage within the previous 21 days, or arterial puncture at a non-compressible site within the previous 7 days; Any known impairment in coagulation due to comorbid disease or anticoagulant use. If on warfarin, then INR >1.7 or prothrombin time >15 seconds; if use of any direct thrombin inhibitors or direct factor Xa inhibitors during the last 48 hours unless reversal of effect can be achieved with a reversal agent; if on any full dose heparin/heparinoid during the last 24 hours or with an elevated aPTT greater than the upper limit of normal; Known defect of platelet function or platelet count below 100,000/mm3 ( but patients on antiplatelet agents can be included ); Ischemic stroke or myocardial infarction in previous 3 months, previous intracranial haemorrhage, severe traumatic brain injury or intracranial or intraspinal operation in previous 3 months, or known intracranial neoplasm, arteriovenous malformation or giant aneurysm; Any terminal illness such that patient would not be expected to survive more than 1 year; Unable to perform CTP or PWI; Hypodensity in >1/3 MCA territory on non-contrast CT; Acute or past intracerebral hemorrhage ( ICH ) identified by CT or MRI; Multiple arterial occlusion ( bilateral MCA occlusion, MCA occlusion accompanied with basilar occlusion ); Pregnant women, nursing mothers, or reluctant to agree taking effective contraceptive measures during the period of trial subjects; Unlikely to adhere to the trial protocol or follow-up; Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study; Participation in other interventional clinical trials within the previous 3 months.