Background <p>Rifampicin-resistant tuberculosis remains a major global health challenge, particularly when occurring as primary resistance in patients without prior tuberculosis treatment. Tuberculosis drug resistance incidence in Indonesia expected 2.2% primary and 25% with prior anti-tuberculosis drug treatment. Resistance of Mycobacterium tuberculosis caused by spontaneous wild type chromosome mutation. Interaction between drug-resistance Tuberculosis and psychiatric disorder were underreported especially in developing countries.</p> Case <p>A 20-year-old female went to Emergency Department with malaise and clinically significant weight loss for the last one month. Fever, cough, and dyspnea were insidious. No prior medical history; lived in rural area with minimal ventilation. Laboratories shown moderate anemia, leukocytosis, and hypo-albumin. Sputum examination using the Xpert MTB/RIF assay detected Mycobacterium tuberculosis with rifampicin resistance. The patient was treated with rifampicin-resistant regimen and evaluated prior treatment with no contraindication. After three days of anti-tuberculosis treatment, patient experienced visual and auditory hallucination. Psychiatry examination conclude schizotypal personality disorder and anti-tuberculosis treatment was save to continue with adjunctive anti-psychotic treatment. After completing the rifampicin-resistant tuberculosis regimen, the patient demonstrated a favourable clinical outcome and was declared cured according to national tuberculosis program criteria.</p> Conclusion <p>Diagnosis of primary rifampicin-resistant pulmonary tuberculosis is a rare diagnosis. During anti-tuberculosis treatment of rifampicin-resistant regimen, close monitoring and evaluation of patient symptoms especially psychiatric disorder should be done. Successful treatment could be achieved with multi discipline approach.</p>