Objective To investigate the application of 320-slice CT whole brain perfusion imaging (CTP) combined with 4D computed tomography angiography (4D-CTA) in the evaluation of collateral circulation in patients with middle cerebral artery (MCA) occlusion. Methods 70 cases of patients with MCA occlusion in the hospital from May 2016 to May 2018 were selected. All patients were given whole brain CTP combined with 4D-CTA. The occlusive side and contralateral cerebral perfusion parameters of MCA occlusion patients were counted. The relative values of collateral circulation open and non-open perfusion parameters were counted in patients with MCA occlusion. The Willis ring and relative values of perfusion parameters of pia mater anastomosis were counted in patients with open collateral circulation. Results The mean transit time (MTT) and maximum peak time (TTP) in occlusive side of MCA occlusion patients were higher than those in contralateral side, and the cerebral blood flow (CBF) and the cerebral blood volume (CBV) were lower than those in contralateral side (P<0.05). The relative cerebral blood flow (rCBF) and the relative cerebral blood volume (rCBV) in open collateral circulation group were higher than those in non-open group (P<0.05). The relative maximum peak time (rTTP) and relative mean transit time (rMTT) of Willis ring group among patients with open collateral circulation were lower than those of pia mater anastomosis group (P<0.05). Conclusion The rCBF and rCBV in MCA occlusion patients with open collateral circulation by 320-slice whole brain CTP combined with 4D-CTA are higher than those in non-open group, and the method can be used to assess the collateral circulation of MCA occlusion patients.