Objective：To explore the curative effects and safety of perospirone combined with thyroxine in the treatment of mental dis－orders caused by primary hypothyroidism. Methods：Totally 34 patients with mental disorders caused by hypothyroidism were treated by perospirone combined with thyroxine（T4）or left-levothyroxine sodium tablets. Positive and negative symptom scale（PANSS） and treatment emergent symptoms scale（TESS） were used to assess the curative effects before and after the treatment. Changes of blood thyroid stimulating hormone（TSH），iodine thyroid acid（T3），T4，free iodine thyroid acid（FT3） and free thyroxine（FT4） before and after the treatment were compared. Results：PANSS total scores were decreased significantly after treatment of perospirone com－bined with T4 or left-levothyroxine sodium tablets，with significant statistical differences before the treatment and at 2，4，8 weeks after the treatment（P<0.01）. Disease efficacy evaluation：the total effective rate was 88.2%. After the treatment，TSH，T3，T4，of FT3 and FT4 were significantly improved compared with those before treatment（P<0.01）. Conclusions：Perospirone is a safe and effective antipsy－chotic medication and can make significant improvement in psychiatric symptoms. Perospirone combined with thyroxine is safe and ef－fective in the treatment of mental disorders caused by primary hypothyroidism.