The frequent occurrences of harmful algal blooms potentially threaten marine organisms. The phycotoxin okadaic acid (OA) has been globally detected in seawater, however, the knowledge of effects of OA on macroalgae is limited. This study investigated the effects of OA (0.01, 0.1 μM) on the growth, physiological and biochemical properties, and transcriptional expression of Pyropia yezoensis. Exposure to 0.1 μM OA for 48 h led to decreased growth, oxidative stress, and lipid peroxidation in P. yezoensis. Levels of reactive oxygen species, glutathione and malondialdehyde, and activity of catalase enzyme were increased, but activity of superoxide dismutase was decreased in P. yezoensis exposed to OA. Even at the low concentration of 0.01 μM, OA influenced the photosynthetic efficiency and stimulated the pigment levels, including phycoerythrin, phycocyanin, allophycocyanin and chlorophyll a. Analytical results of amino acids indicated that OA reduced the nutritional quality of P. yezoensis. The expression of genes involved in nitrogen metabolism was up-regulated, but the genes associated with ABC transporters and photosynthesis was down-regulated by the OA exposure, suggesting that OA may affect photosynthesis and enhance nitrogen uptake and assimilation processes. This study provides a new perspective on the chemical ecology risk of phycotoxins to marine macroalgae.