Background: Secondary hyperparathyroidism (SHPT), a manifestation of chronic kidney disease-mineral bone disorder (CKD-MBD), is common in CKD patients and has significant morbidity and mortality. Quality of life (QOL) in SHPT patients is seriously affected by symptoms such as bone pain and skin pruritus. However, studies have focused on operative effects and hypocalcemia rather than the relationships between QOL, bone pain, skin pruritus and depression symptoms.Methods: A cross-sectional survey was conducted from January 2017 to December 2019 in a third-class hospital in China. The brief table of the QOL measurement scale (QOL-BREF), a self-designed bone pain and skin pruritus scale and the Self-rating Depression Scale (SDS) were used to estimate QOL, bone pain and skin pruritus, and depression, respectively. Pearson’s correlation, multiple linear regression analysis and structural equation modeling (SEM) were used for analysis.Results: Overall, 320 questionnaires were considered valid (98.46% effective response rate). The prevalence of bone pain, skin pruritus and depression was 94.06%, 69.06%, and 77.81%, respectively. Bone pain, skin pruritus and depression were significantly associated with QOL. In SEM, QOL negatively correlated with bone pain (r=-0.509), skin pruritus (r=-0.517) and SDS (r=-0.465). Bone pain significantly (P<0.01) and positively correlated with skin pruritus (r=0.568) and SDS (r=0.450). Skin pruritus significantly (P<0.01) and positively correlated with SDS (r=0.426). In addition, QOL partially mediated the association between bone pain or skin pruritus and depression (mediation proportion of 48.62% or 45.08%).Conclusions: Patients with SHPT undergoing Parathyroidectomy(PTX) have high depression levels and poor QOL due to bone pain and skin pruritus. The effects on depression may be fully mediated by the impact of bone pain or skin pruritus on QOL. Thus, bone pain or skin pruritus could increase depression via the intermediary role of QOL.For clinical front-line medical staff,it can relieve bone pain and skin pruritus through timely operation and psychological intervention, so as to improve patients' quality of life and reduce anxiety.At the same time, we should also pay attention to the high-risk groups.