Abstract Background Pituitary adenomas (PAs) are prevalent tumors that often exhibit ischemia, hypoxia, and cystic transformations, impacting their prognosis. The relationship between cystic degeneration in PAs and the expressions of hypoxia-inducible factor-1α (HIF-1α), glucose transporter 1 (GLUT1), and Ki-67 remains unclear. This study aims to analyze the correlation between MRI characteristics of cystic PA and the expression of these proteins. Methods This is a retrospective analysis. A total of 74 patients with cystic PA and 30 PA patients without cystic degeneration were enrolled. Their MRI signs were analyzed. According to the T2WI signs of PA, they were divided into the fluid level group (n = 26), non-fluid level group (n = 48), and non-cyst group (n = 30). Immunohistochemistry was performed to evaluate the expression levels of HIF-lα, GLUT1, and Ki-67 protein. Univariate and multinomial logistic regression analyses were used to evaluate the factors affecting MRI signs of PA. Spearman correlation was also performed. Results There was no significant difference in gender, age, and HIF-1α protein expression among the three groups. Significant differences were found in invasiveness (P = 0.008), GLUT1 (P