Various nanomaterials are used as food additives, medicines, and cosmetics; however, their biological effects are not completely understood. Since the cell membrane is the first point of contact between nanomaterials and cells, we investigated whether amorphous silica particles and titanium dioxide nanoparticles (nTiO2) interact with the transporters present in the cell membrane. In this study, we prepared an adriamycin (ADM) resistant variant of the mouse lymphocytic leukemia cell line L1210 (L1210/ADM). Since our L1210/ADM cells were confirmed to excrete ADM in a P-glycoprotein (P-gp)-dependent manner, we investigated whether nano- and micro-sized amorphous silica particles (nSP and mSP) and nTiO2 inhibited ADM excretion from L1210/ADM cells. Both nSP and nTiO2 inhibited ADM efflux in a dose-dependent manner; however, mSP did not inhibit ADM efflux even at the highest dose (0.25 mg/mL). These results suggest that nSP and nTiO2 interfere with P-gp, which is involved in ADM transport, and L1210/ADM cells are suitable for safety screening tests of nanomaterials.