Background/Aims: As a model organism for a pleiomorphic marine planktonic primary producer, Phaeodactylum tricornutum has been studied on a molecular level under diverse cultural conditions. But little is known about its morphological, nutritional or transcriptomic responses under grazing stress. Methods: To assess microalgal molecular and cellular responses to grazer presence, we conducted transcriptome profiling in combination with growth rate, biovolume, fatty acid content, carbon and nitrogen content measurements in the model diatom Phaeodactylum tricornutum. RNA-sequencing was used to evaluate the transcriptomic response to grazing stress for P. tricornutum strain CCAP 1055/1. Results: Among the differentially expressed genes, we found down-regulation of genes involved in pathogen resistance, and in fatty acid biosynthesis pathways, while mitosis-involved genes were up-regulated. Experimentally testing morphological and biochemical responses in five strains of the species, we detected strain-specific significant effects of simulated grazing pressure in altered growth rates, biovolume and nutritional composition. Conclusion: Our research reveals the associated molecular and cellular responses to grazing effects in P. tricornutum and extends the understanding of co-evolutionary roles in regulating grazing defence between P. tricornutum and its grazer.