This dissertation is presented in two sections. Section one recounts my investigations of modulating the multidrug-resistant protein-three (MRP3) levels, by either activating or silencing the transcription factor Nrf2, in normal lung cells and Keap1 wild-type and mutant non-small cell lung carcinoma cell lines (NSCLC). In section two direct interactions between Nrf2 and the MRP3 promoter were evaluated in NSCLC. Additionally, the relationships between MRP3 mRNA levels and Keap1, Nrf2, and p53 status were also investigated in cell lines and tumor specimens. Combined, these sections explore the complex regulation of the MRP3 gene.