Background: Thyroidectomy has been considered an effective method to treat thyroid cancer. However, about 20% of patients have psychological distress before surgery. Psychological distress is considered common mental illnesses and it has been reported that the patients who suffer psychological distress have poor clinical outcomes than the patients without psychosocial disorder. Therefore, we design this randomized controlled study to explore the effect of psychological nursing intervention against quality of life and psychological distress of the patients with thyroid cancer. Method: The trial will be conducted from September 2020 to December 2020 at Wuhan Fourth Hospital on the basis of the International Council for Harmonisation's Good Clinical Practice Guidelines and the principles of the Helsinki Declaration. The study was authorized via the Research Ethics Committee of the Wuhan Fourth Hospital (Approval number: 20200721-046). This study is a single-center, randomized, 2-arm, evaluator-blinded clinical trial. In all, 90 patients with thyroid cancer undergoing thyroidectomy will be enrolled in this study. The inclusion criteria includes: patients aged between 20 and 60 years old; ASA I-II classification; normal platelet coagulation and count function. The exclusion criteria contains: people with the intellectual and cognitive impairment (behavioral-cognitive intervention); BMI above 35 kg/m 2 ; the history of renal and hepatic dysfunction; and patients refuse to participate in this study. Both the patients in psychological intervention group and control group should receive the routine care, while the psychological intervention group also needs to receive the additional proper psychological nursing interventions. The emotional disorders are detected with the Chinese version of Profile of Mood States-Brief. And the patients’ life quality is evaluated with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire (QLQ-C30, version 3.0). All the data are collated into Microsoft Excel 2010 and analyzed with SPSS 12.0 (IBM). Results: It is assumed that psychological nursing intervention could alleviate the psychological distress of patients with thyroid cancer and improve their quality of life. Conclusion: This study can provide the reliable evidence regarding the influence of psychological nursing intervention against the life quality and psychological distress of the patients with thyroid cancer. Trial registration: This study protocol is registered in Research Registry (researchregistry5937).