Background Terminalia avicennioides Guill and Perr (Combretaceae) is an important West African medicinal plant. The plant is used locally against microbes and parasites in both humans and animals and studies have demonstrated its cytotoxicity potential. Thus, this study was carried out to test the cytotoxic effect of the extracts and fractions of the root of the medicinal plant Terminalia avicennioides Guill and Perr (Combretaceae) in two different cell lines. Methods Methanol, ethanol, 30 % ethanol, hot water and cold water extracts and ethylacetate, hexane, chloroform, butanol and residual water fractions, were evaluated at 1000, 750, 500, 250, 100 and 50 µg/mL concentrations, with doxorubicin as positive control. The cells were incubated with the extracts for 48 h at 37 °C in a 5 % CO2 humidified incubator. The inhibition of cell viability, determined with the methyl blue thiazole tetrazolium bromide (MTT) assay, was used to assess the anti-proliferative effect of the extracts, in normal Vero Monkey kidney and human liver cancer (HepG2) cell lines. Results There was a concentration-dependent inhibition of cell viability in both the HepG2 and Vero cell lines. For HepG2 cells, antiproliferative effect was highest for the hexane fraction (viability ranged from 19.63 ± 1.10 % to 70.30 ± 1.78 % for 1000 and 50 µg/mL, respectively. For Vero cells, the highest antiproliferative effect, at 1000 µg/mL, was with hexane fraction (cell viability 21.37 ± 3.50 %), while at 50 µg/mL the chloroform fraction demonstrated the highest effect (viability of 86.10 ± 1.95 %). Conclusions The extracts and fractions from the root of Terminalia avicennioides have antiproliferative effect on the Vero and HepG2 cell lines tested. However, the extracts and fractions were not more toxic to the HepG2 than to the Vero cells. The cytotoxic effect of stem-bark and leaf extracts could be evaluated in the future to determine its anticancer potential.