Microcystin-LR (MC-LR), the most prevalent and poisonous type of microcystins (MCs), is generated by the widespread occurrence of cyanobacterial blooms. MCs can enter farmland through irrigation water and will inevitably produce negative effects on terrestrial plants. However, little is known about the molecular toxic processes behind the programmed cell death (PCD) induced by MCs in plants. In the current study, the effects on the viability, oxidative stress, and expressions of PCD-related genes in rice suspension cells were investigated under the MC-LR exposure at different concentrations (5.00, 50.0 and 500 μg L−1). A kinetic model based on the sGompertz growth equation could be used to well fit the growth curve of suspension cells. More than 0.5 days of exposure to MC-LR significantly reduced the cells viability in all treatment groups. MC-LR has a dualistic effect on O2•− and GSH levels in rice cells due to the antioxidant system responses and subcellular damages. Upregulated of the transmembrane protein-encoding gene OsOATPM in cells under MC-LR exposure indicates its involvement in transporting MC-LR. MC-LR treatment could induce significant expression of OsPDCD5 gene (an ortholog to mammalian-programmed cell death 5) and metacaspase family gene OsMC-6 in rice suspension cells, but inhibit the expression of the vacuolar processing enzyme (VPE) family genes OsVPE-1 and OsVPE-2. Taken together, MC-LR induces PCD in rice suspension cells, mediated by production of ROS, might primarily through the influence of metacaspase family gene OsMC-6 expression. A reduction in mitochondrial ATP levels under the regulation of mitochondrial energy related gene Os03g278900 might also occur during the MC-LR-induced PCD process.