The positive response to tamoxifen in ERα-positive breast cancer patients is usually of a short duration as many of the patients eventually develop resistance. Our preliminary results show that aloe emodin extracted from the leaves of the Aloe barbadensis Miller demonstrated a cytotoxicity that is selective to ERα-positive breast cancer cells (MCF-7), but not to ERα-negative breast cancer cells (MDA-MB-231) and to the control cells (MCF- 10A). The objective of this study was to test the hypothesis that aloe emodin may enhance the response of MCF-7 cells to treatment with tamoxifen. MCF-7 cells were treated with aloe emodin alone, tamoxifen alone or a combination of emodin and tamoxifen, at their respective IC concentrations and at different time points of 24 hours, 48 hours and 72 hours. The respective IC were the concentrations of aloe emodin and tamoxifen required to achieve 50% inhibition of the cells in the study. Cell viability and apoptosis were determined using trypan blue exclusion and DNA fragmentation assays, respectively. The involvement of RAS/MEKs/ERKs genes of MAPK signalling pathways with aloe emodin was determined using QuantiGene 2.0 Plex assay. Data was evaluated using the one-way ANOVA test. Our findings showed that aloe emodin enhanced the cytotoxicity of tamoxifen on MCF-7 cells through apoptosis by downregulation of MEK1/2 genes. Our research may provide a rational basis for further in vivo studies to verify the efficacy of a combination of aloe emodin and tamoxifen on the viability of ERα-positive-breast cancer cells.