Sulfitobacter porphyrae ZFX1, isolated from surface seawater of the East China Sea during a Prorocentrum donghaiense bloom recession, exhibits high algicidal activity against P. donghaiense. To evaluate the algicidal effect of ZFX1, the algicidal mode and stability were investigated. The results showed that ZFX1 indirectly attacked algae by secreting algicidal compounds, and the algicidal activity of the ZFX1 supernatant was insensitive to different temperatures, light intensities and pH values (pH 3–12). To explore the algicidal mechanism of the ZFX1 supernatant, its effects on the morphological and ultrastructural alterations, photosynthetic capacity, reactive oxygen species (ROS) and antioxidative system of P. donghaiense were investigated. Scanning and transmission electron microscopy revealed that the ZFX1 supernatant destroyed the algal cell membrane structure and caused intracellular leakage. The decrease in the chlorophyll a content and the marked declines in both the photosynthetic efficiency (Fv/Fm) and the electron transport rate (rETR) indicated that the ZFX1 supernatant could damage the photosynthetic system of P. donghaiense. The excessive production of ROS in algal cells demonstrated the oxidative damage triggered by the ZFX1 supernatant. Although the antioxidant defense system of P. donghaiense was activated to scavenge excessive ROS, lipid oxidation occurred. The fatty acid composition profile indicated that the ZFX1 supernatant markedly increased the contents of two saturated fatty acids and a monounsaturated fatty acid and decreased the proportion of two polyunsaturated fatty acids, which resulted in lipids with a lower degree of unsaturation (DU). The decline in the DU decreased the lipid fluidity and rigidified the membrane system, and these effects destroyed the function of the membrane system and ultimately resulted in algal cell death. Therefore, ZFX1 probably plays a key role in mitigating P. donghaiense bloom by inducing lipid oxidation, decreasing the DU of lipids and ultimately destroying the membrane systems of algal cells.