Objective：To explore the efficacy and safety of individualized selection of chemotherapy drug guided by excision repair cross complement group1（ERCC1），ribonucleotide reduc tase 1（RRM1） and tubulin beta 3（TUBB3） in patients with advanced non-small cell lung cancer（NSCLC）. Methods：Totally 47 cases of advanced NSCLC were divided into individualized chemotherapy treat－ment group（group A） and control group（group B） according to histopathological tissue sufficient or not. In group A，mRNA levels of ERCC1，RRM1 and TUBB3 were measured by branched DNA-liquid chip technique and chemotherapy regimen was formulated ac－cording to the measured results. Group B were treated by gemcitabine plus cisplatin. Results：Effective rate of group A was 63.2%，significantly higher than that of group B（P<0.05）. Disease control rates of group A and group B were 78.9% and 50.0% respectively（P<0.05）. Effective rate was significantly higher in patients treated by gemcitabine plus cisplatin in group A than in patients received the same treatment in group B. Quality of life in both groups was improved significantly after treatment（P<0.05） than before treat－ment，but there was no significant difference in improvement rate（P >0.05）. There was no difference in adverse reactions between both groups and all patients were well tolerated. Conclusions：Determination of mRNA levels of ERCC1，RRM1 and TUBB3 by branched DNA-liquid chip technique can guide individualized chemotherapy for advanced NSCLC and significantly improve chemotherapy efficiency； however，further exploration of more effective individualized treatment plan is needed.