Abstract： Objective To explore the relationship between imatinib resistance and genes MDR1 and KIT in gastrointestinal stromal tumor(GIST) cells. Methods The MDR1 and KIT mRNA level in GIST882-R and GIST882-S cells were detected by RT-PCR. Immunocytochemistry and Western blot were employed to detect P-gp and CD117 expression in GIST882-R and GIST882-S cells. Results The relative expression of MDR1 mRNA was 0.321 ±0.033 in GIST882-R and 0.157 ±0.056 in GIST882-S cells, and the difference was statistically significant (P<0.05). The relative expression of KIT mRNA was 0.389 ±0.063 in GIST882-R and 0.339 ±0.067 in GIST882-S, and the difference was not statistically significant (P>0.05). The relative density of P-gp was 0.443±0.058 in GIST882-R and 0.237±0.094 in GIST882-S, and the difference was statistically significant (P<0.05). The relative density of CD117 was 0.744±0.123 in GIST882-R and 0.704±0.094 in GIST882-S, and the difference was not statistically significant (P>0.05). Conclusions Over-expression of gene MDR1 may be associated with imatinib resistance in GIST. KIT may not be involved in imatinib resistance.