Abstract: Background: Mucoxinis believed to be a promising anticancer because it is known to inhibit cell proliferation. However, given study on mucoxin still very limited, the mechanism of the substances isolated from leaf extract of Rollinia mucosa in regulating and eliminating cancer cells has not fully understood. This study investigated the mucoxin mechanism in affecting proliferation, expression of p53 and cyclin D1 genes in the T47D breast cancer cells. Materials and Methods: The cell line samples were grouped into four referred to the hour of assays undertaken after mucoxin application, namely hour 0th, 24th, 48th and 72nd. Each group was given mucoxin of six different concentrations namely 0.00 μg mL–1 as a control, 0.1×10–3, 0.5×10–3, 1×10–3, 5×10–3 and 10×10–3 μg mL–1 with three replications. Cells proliferation assayed by flow cytometry technique using BrDU staining protocol, whereas the expression of p53 and cyclin D1 genes determined by quantitative PCR (qPCR). Results: Cell proliferation in each group significantly reduced by mucoxin treatment. Mucoxin enhance p53 gene expression in 48 h, while the expression of cyclin D1 supressed signifantly by mucoxin of 5×10–3 and 10×10–3 μg mL–1 in 48 and 72 h. Simple regression analysis showed that cell proliferation decreased with the increase of p53 expression and the suppression of cyclin D1 gene, while p53 expression positively associated to cyclin D1 expression. Conclusion: Mucoxin can decrease the proliferation of T47D breast cancer cells by suppressing the expression of cyclin D1 mediated by p53 gene.