Phycotoxins severely threaten ecosystem stability and public health, but how the presence of phycotoxins could affect the diversity, assembly and biointeractions of plankton communities remains elusive. Here, we used metabarcoding techniques to characterize the community assembly and co-occurrence network of microeukaryotic plankton and their associated prokaryotes in the Pearl River Estuary (PRE) where homo-yessotoxin (hYTX) and pectenotoxin-2 (PTX2) were detected. Results showed the planktonic microbiome was distinctly separated by the cell abundance of toxic algae, while the community diversity was less affected. Microeukaryotic plankon was dominated by Bacillariophyta and Dinophyceae, and their associated prokaryotes were dominated by Gammaproteobacteria and Alphaproteobacteria. Generally, temperature, salinity, phycotoxin concengtation and cross-domain biointeractions co-shaped the planktonic microbiome with microeukaryotes more sensitive to environmental filtering. The community was mainly determined by stochastic processes (dispersal limitation and ecological drift) but the contribution of deterministic processes to prokaryotic community was greater than that to microeukaryotic community. Further analysis on the subcommunities with different abundance revealed that abundant taxa was widespread, while rare taxa was habitat-specifics. Over 75% of the interactions in the co-occurrence network and 44 out of 56 keystone OTUs belonged to moderate or rare taxa, suggesting that non-abundant taxa played a critical role in maintaining ecosystem stability and functions. Most frequent and strong interactions were detected among Bacillariophyta, Dinophyceae, Syndiniales, Proteobacteria and Planctomycetes. Overall, these findings expand current understanding of the ecological mechanisms and microbial interactions in changing ecosystems where marine phycotoxins were detected.