Primary hyperparathyroidism (PHPT) might associate with multiple neuropsychiatric symptoms, but it is often overlooked by physicians when making differential diagnosis for patients with psychiatric disorders. We report a case of PHPT presenting as major depression with psychotic features. A 47-year-old previously healthy woman presented with a 2-weeks history of depressed mood, loss of interest, insomnia, poor concentration, fatigue and poor appetite with prominent body weight loss. Besides, blunted affect, prominent psychomotor retardation, occasional irrelevant speech, the delusion of guilt, persecution, and negation were also noted. Under the impression of major depressive disorder, she was treated with escitalopram >20 mg and aripiprazole 10 mg per day. After drug treatment for four weeks, the score of the 17-item Hamilton Depression Rating Scale (HAMD-17) was decreased from the initial 46 to 35, which didn’t reach obvious response (defined by a decrease of scores for 50% or more). The following laboratory tests revealed severe hypercalcaemia of 16.8 (reference, 8.6-10.0) mg/dl, hypokalemia of 2.4 (3.5-5.1) mg/dl, borderline thyroid function with free-T4 of 1.74 (0.93-1.7) ng/dl and thyroid-stimulating hormone of 1.18 (0.27-4.2) μIU/ml, along with blood urea nitrogen of 26.2 (6-20) mg/dl and creatinine of 1.4 (0.5-0.9) mg/dl.