Cytotoxic activity of artemisinin and derivatives in the presence and absence of holo-transferrin andexpression of genes involved in resistance of cancer cells were investigated in human cholangiocarcinoma (CL-6)and hepatocarcinoma (Hep-G2) cell lines in vitro. After incubation with the test drugs and 5-fluorouracil (5-FU) cytotoxicity was asessed by MTT assay. RNA was extracted after 24 hour exposure to holo-transferrin forinvesstigation of the expression of transferrin receptor 1 (TDR1), multidrug resistance 1 (MDR1), multidrugresistance protein 1 (MRP1), multidrug resistance protein 2 (MRP2), and multidrug resistance protein 3 (MRP3).The median IC50 of artemisinin, artesunate, β-artemeter, dihydroartemisinin and 5-FU were as follows: CL-6:339, 131, 354, 75, and 377 μM, respectively; Hep-G2: 268, 50, 233, 29, and 1,380 μM. Exposure to holo-transferrinhad no influence on sensitivity of either cell line to artemisinin derivatives, but resulted in a 3-fold increase inthe expression of TR1 and MDR1, and a 2-fold increase in the expression of MRP1 and MRP2 in CL-6 cells.With Hep-G2, a 3-fold increase in the expression of MDR1 and MRP3 and a 2-fold increase in expression ofMRP2 were observed. Dihydroartemisinin exhibited the most potent cytotoxic activity against both cell linesand holo-transferrin caused different patterns of expression of resistance-associated genes.