Objective Pituitary adenomas (PAs) not only cause physiological symptoms, but also lead to psychological symptoms, which result in the decline of the quality of life (QOL) ultimately. This study aims to identify the factors that might influence the QOL of patients with PAs before and after endoscopic transsphenoidal surgery (ETSS). Methods A total of 83 patients with PAs who underwent ETSS and completed the visual-related QOL (VR-QOL), headache impact test (HIT-6), Hamilton anxiety/depression rating scale (HAMA/HAMD), and 36-items health-related QOL (HR-QOL) questionnaires preoperatively and at 1/3 months postoperatively were recruited. According to the preoperative physiological/psychological HR-QOL, they were divided into four groups. And, the factors that might be correlated with the impairment of physical/psychological QOL before ETSS and the improvement of physical/psychological QOL after ETSS were identified by comparative and regressive analysis in terms of gender, age, tumor size, pathological type, VR-QOL, HIT-6, HAMA and HAMD. Results As for the patients with PAs before ETSS, the degree of physiological QOL impairment was positively correlated with VR-QOL and was negatively correlated with HIT-6 and HAMD score, while the degree of psychological QOL impairment was positively correlated with age and was negatively correlated with HIT-6, HAMA and HAMD score. After those patients underwent ETSS, they gradually acquired the improvements of physiological and psychological QOL from 1 to 3 months, which were positively correlated with the increased value of VR-QOL and the decreased value of HIT-6, HAMA and HAMD scores. Conclusions The impairment of HR-QOL before ETSS and the improvement of HR-QOL after ETSS in patients with PAs were closely correlated with headache, subjective perception of vision and visual field loss, and the anxiety/depression emotions.