[Objective] To investigate the preliminary clinical efficacy of Xpert MTB/RIF guided individualized chemotherapy for the treatment of Rifampicin-resistant/Multi-drug resistant tuberculosis. [Methods] A total of 120 cases of spinal tuberculosis admitted to the Eighth Medical Center of PLA General Hospital from June 2017 to June 2018 and meeting the inclusion criteria were enrolled in. All the 120 patients had successfully underwent surgery. After the surgery, the individualized chemotherapy regimen was formulated with reference to the previous anti-tuberculosis chemotherapy history and Xpert MTB/RIF test results, and the chemotherapy regimen was adjusted again according to the results of phenotype drug sensitivity results. Follow-up was conducted at 1, 2, 3, 6, 9, and 12 months after the surgery, followed up at an interval of 6 months. X-ray, CT, 3D reconstruction, MRI and other imaging data and laboratory indicators were collected to evaluate the fusion of bone graft and inflammatory activity. [Results] Among the 120 patients, 79 （65.83%）Xpert MTB/RIF tested positive for mycobacterium tuberculosis, and 48 (40.00%) tested positive for mycobacterium BACTEC MGIT 960 liquid culture system, with statistically significant difference (2=15.05, P=0.0001). Xpert MTB/RIF detected 11 cases of rpoB gene mutation, among which 6 cases of phenotypic drug sensitivity proved rifampicin resistance, while 1 case of Xpert MTB/RIF tested negative proved rifampicin resistance. At each postoperative follow-up point, erythrocyte sedimentation rate and C-reactive protein gradually decreased to normal levels in 11 patients. Liver function damage was found in 3 patients and hyperuricemia was found in 5 patients, all of which were improved after symptomatic treatment. Bone fusion was achieved at the final follow-up, with an average fusion time of 5.6 months. There was no complications such as sinus, cold abscess, implant failure and pseudarthrosis. [Conclusion] The individualized chemotherapy regimen based on Xpert MTB/RIF is conducive to the early cure of Rifampicin-resistant/Multi-drug resistant tuberculosis and the resolution of severe complications.