Objective To identify the relations of secondary cerebral edema volume with aquaporin 4 (AQP4) and reactive oxygen species (ROS) levels in patients with spontaneous deep supratentorial intracerebral hemorrhage. Methods Forty-seven patients with spontaneous deep supratentorial intracerebral hemorrhage, admitted to our hospital from December 2016 to January 2018, were chosen in our study; on the 1st, 3rd, 14th and 28th d of onset, the hematoma volume and secondary cerebral edema volume were measured by CT scan. Serum AQP4 and ROS levels were measured by ELESA. The relations of perihematomal edema volume with AQP4 and ROS levels in patients with spontaneous deep supratentorial intracerebral hemorrhage were analyzed. Results The hematoma volumes on 14th and 28th d of onset were significantly decreased as compared with those on 1st and 3rd d of onset (P<0.05); the serum AQP4 and ROS levels gradually increased on 1st, 3rd, and 14th d of onset, with significant differences (P<0.05). The cerebral edema volume, and serum AQP4 and ROS levels on 28th d of onset were significantly decreased as compared with those on 3rd and 14th d of onset (P<0.05). Serum AQP4 and ROS levels were positively correlated with cerebral edema volume (r=0.331, P=0.000;r=0.541, P=0.000); serum ROS level was positively correlated with AQP4 level (r=0.298, P=0.000). Conclusion The changes of brain edema volume, and serum AQP4 and ROS levels in patients with spontaneous supratentorial intracerebral hemorrhage are consistent and positively correlated, which suggests that the antioxidant may reduce the AQP4 protein expression, reduce the degree of brain edema, and alleviate the deterioration of patients with spontaneous intracerebral hemorrhage.