【Objective】To investigate whether excision repair cross-complementing rodent repair deficiency gene 2 (ERCC2）expression correlates with drug resistance in human tumor cell lines utilized by the anticancer drug screening program of the National Cancer Institute (NCI).【Methods】With Western blot analysis,ERCC2 protein levels of 60 human tumor cell lines were determined and compared with the patterns of cytotoxicity (determined by sulforhodamine-B assay) of 170 anticancer drugs.【Results】ERCC2 protein levels had a wide range of expression including undetectable levels in 6 cell lines.ERCC2 protein levels were found to be significantly correlated with resistance of the tumor cells to 28 out of 170 chemotherapeutic agents.Considering the mechanism of action,ERCC2 expression was significantlyrelated toresistance of thetumor cells toalkylatingagents or tubulin-active antimitotic agents.【Conclusion】The present study suggests that ERCC2,and perhaps NER in general,is a contributing factor to alkylating agents and tubulin-active antimitotic agents resistance in human tumor cell lines.