Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer deaths worldwide. The anticancer drugs being used are losing their effectiveness due to development of anticancer-drug resistance and have severe side effects, poor therapeutic index and high cost. This work was designed to study the anticancer effect of new monocationic arylthiophene derivatives against HCC. The cell viability was initially determined by treating Huh-7 cells with 50 µM concentration of each tested arylthiophene compound. Subsequently, the IC₅₀ values for the most active compounds were determined using MTT assay. The monocationic derivative 2j exhibit the highest cytotoxicity (IC₅₀ = 1.47 ± 0.25 µM) in comparison to the positive control cisplatin (IC₅₀ = 24.9 ± 1.4 µM). The selectivity index of compound 2j (SI = 7.25 ± 0.11) proved the safety to normal lung fibroblast cells (WI-38) vs Huh-7 cells