Diatom bloom is characterized by a rapid increase of population density. Perception of population density and physiological responses can significantly influence their survival strategies, subsequently impacting bloom fate. The population density itself can serve as a signal, which is perceived through chemical signals or chlorophyll fluorescence signals triggered by high cell density, and their intracellular signaling mechanisms remain to be elucidated. In this study, we focused on the model diatom, Phaeodactylum tricornutum, and designed an orthogonal experiment involving varying cell densities and light conditions, to stimulate the release of chemical signals and light-induced chlorophyll fluorescence signals. Utilizing RNA-Seq and Weighted Gene Co-expression Network Analysis, we identified four gene clusters displaying density-dependent expression patterns. Within these, a potential hub gene, PtSLC24A, encoding a Na+/Ca2+ exchanger, was identified. Based on molecular genetics, cellular physiology, computational structural biology, and in situ oceanic data, we propose a potential intracellular signaling mechanism related to cell density in marine diatoms using Ca2+: upon sensing population density signals mediated by chemical cues, the membrane-bound PtSLC24A facilitates the efflux of Ca2+ to maintain specific intracellular calcium levels, allowing the transduction of intracellular density signals, subsequently regulating physiological responses, including cell apoptosis, ultimately affecting algal blooms fate. These findings shed light on the calcium-mediated intracellular signaling mechanism of marine diatoms to changing population densities, and enhances our understanding of diatom bloom dynamics and their ecological implications.