Background: Docetaxel (Taxotere(R)) has been known as one of the most active anti-cancer drugs for breast, ovary, head and neck, prostate, and NSCLC. Neutropenia and asthenia are the toxic reactions frequently observed during docetaxel treatment. We carried out the association study between docetaxel-related toxicities, tumor response and genetic polymorphisms of CYP3A4, CYP3A5, ABCC2, and SLCO1B3. Method: Clinical information was collected from 54 advanced or metastatic NSCLC patients who received docetaxel containing chemotherapy. We extracted genomic DNA from periphreal blood and genotyped CYP3A4 (CYP3A4*1B, CYP3A4*18, CYP3A4*3), CYP3A5(CYP3A5*2, CYP3A5*3), ABCB1 (C1236T, G2677T/A, C3435T), SLCO1B3 (rs11045585), ABCC2 (rs12762549) using direct sequencing and pyrosequencing. Result: Mean age was 59.8 (35-78) yrs and M:F ratio was 41:13. Fifty pts (92.6%) were in ECOG performance status 0-1. Fifty three pts (98.1%) were stage III or IV. Forty six pts (85.2%) received more than 60 mg/m2 of docetaxel. Objective response rate (CR+PR) was 42.6%. Fifteen pts (27.8%) were still in SD and 14 pts (25.9%) showed PD. Severe neutropenia (G3-4) occurred in 33 pts (61.1%). Mild to moderate leukopenia, anemia and thrombocytopenia (G1-2) were observed in 21 (39.8%), 47 (87.0%) and 14 (25.9%) pts. Asthenia occurred in 34 pts (63.0%) and G2-3 asthenia occured in 19 pts (35.2%). Genetic variants of CYP3A4 (CYP3A4*1B, CYP3A4*18, CYP3A4*3) and CYP3A5*2 were not found. Statistically significant associations existed between G2677T/A, ABCC2 and severe leukopenia (p=0.025, p=0.028) as well as between C3435T and neutropenia (p=0.029), anemia (p=0.044). Significant associations between tumor response and G2677T/A (OR=4.54) and SLCO1B3 (OR=9.44) were observed. Conclusion: Taken together, our data suggest that G2677T/A (MDR1) and SLCO1B3 may be major pharmacogenetic predictors for severe hematologic toxicities and tumor response in advanced NSCLC patients receiving docetaxel containing chemotherapy.