Ecological risk of micro/nano-plastics (MPs/NPs) has become an important environmental issue. Microcystin-leucine-arginine (MC-LR) produced by Microcystis aeruginosa (M. aeruginosa) is the most common and toxic secondary metabolites (SM). However, the influencing mechanism of MPs and NPs exposure on MC-LR synthesis and release have still not been clearly evaluated. In this work, under both acute (4d) and long-term exposure (10d), only high-concentration (10 mg/L) exposure of amino-modified polystyrene NPs (PS-NH2-NPs) promoted MC-LR synthesis (32.94 % and 42.42 %) and release (27.35 % and 31.52 %), respectively. Mechanistically, PS-NH2-NPs inhibited algae cell density, interrupted pigment synthesis, weakened photosynthesis efficiency, and induced oxidative stress, with subsequent enhancing the MC-LR synthesis. Additionally, PS-NH2-NPs exposure up-regulated MC-LR synthesis pathway genes (mcyA, mcyB, mcyD, and mcyG) combined with significantly increased metabolomics (Leucine and Arginine), thereby enhancing MC-LR synthesis. PS-NH2-NPs exposure enhanced the MC-LR release from M. aeruginosa via up-regulated MC-LR transport pathway genes (mcyH) and the shrinkage of plasma membrane. Our results provide new insights into the long-time coexistence of NPs with algae in freshwater systems might pose a potential threat to aquatic environments and human health.