Abstract: Objective: To investigate the relationship between the expressions of human tubulin beta-3 Chain( -Tubb3), ribonucleotide reductase 1( RRM1) and excision repair cross compementation 1( ERCC1) in stage Ⅲb / Ⅳ non-small cell lung cancer( NSCLC) and treatment effects with gemcitabine,taxanes and platinum. Methods: Four hundred and eighty patients with stage Ⅲb/Ⅳ NSCLC were randomly divided into the test group and control group( 240 cases each group). The mRNA expressions of RRM1,-Tubb3 and ERCC1 in paraffin-embedded tissue sample from the test group were detected using fluorescence quantitative-HRM method,the patients from the test group were treated with GP,NP,TP or cis-platinum combined with Pemetrexed chemotherapy regimens according to their RRM1 and -Tubb3 expressions levels,respectively. The control group were treated with a random chemotherapy regimen. The chemotherapeutic effects and overall survival of two groups were observed. Results: The objective response rates in test group and control group were 66. 1% and 31. 7%,respectively. The disease control rates in two groups were 79. 7% and 46. 3%,the difference of which was statistical significance( P 0. 01). The overall survival in two groups were 11. 2 months and 9. 8 months,the difference of which had no statistical significance( P 0. 05). The objective response rate in test group treated with GP program( 70. 7%) was significantly higher than that in the control group( 32. 6%)( P 0. 01),the objective response rate in test group treated with NP and TP program( 66. 7%) was significantly higher than that in the control group( 29. 5%)( P 0. 01). The objective response rates in test group with low and high ERCC1 expressions were78. 7% and 50. 9%,respectively,the difference of which had statistical significance( P 0. 01). The overall survival in test group with low and high ERCC1 expressions were 11. 4 months and 10. 9 months,respectively,the difference of which had no statistical significance( P 0. 05). Conclusions: The expression levels of RRM1 and -Tubb3 in patients with stage Ⅲb/Ⅳ NSCLC can guide the selecting of chemotherapy regimen,which can significantly increase the response rate.