Abstract: Objective To investigate the effect of comprehensive nursing intervention on rehabilitation and treatment compliance in elderly hypothyroidism patients with depression. Methods 78 cases of elderly hypothyroidism patients with depression were randomly divided into study group (39 cases) and control group (39 cases) according to the random number table method. The all patients were treated with conventional drug treatment, the control group was treated with the routine nursing care and the study group was treated with comprehensive nursing intervention. The rehabilitation effect and treatment compliance of two groups were evaluated. Results After the nursing intervention, the SAS, SDS, NFA and ALD score in study group were 40.23±4.32, 53.55±6.32, 12.33±1.98 and 44.34±4.12 respectively; and they were significantly improved compared with the pre-intervention and control group (P<0.05). The serum levels of TT4, FT3, TT3, FT4 and TSH in study group after nursing intervention were significantly improved compared with those before intervention and control group (P<0.05), and were then recovered to the normal level. After the intervention, the treatment compliance in study group was improved significantly than that in control group (P<0.05). Conclusion Comprehensive nursing intervention could promote the rehabilitation and medication compliance in elderly hypothyroidism patients with depression, and it is worthy for clinical application.