The blades of intertidal red algae Pyropia haitanensis can lose 90% cellular water during low tides, thus is a good material for exploring mechanisms of tolerance to intertidal desiccation. Here, multi-omics responses of blades to a single stress of desiccation (SS) or triple stress containing desiccation, high-temperature and high-light (TS) were determined. Differentially expressed genes (DEGs) and proteins (DEPs), and accumulated metabolites (DAMs) were analyzed in pairs. The results showed that several DEGs/DEPs, DEGs/DAMs, and DEPs/DAMs participated in Glyoxylate and dicarboxylate metabolism (ko00630) and Carbon fixation in photosynthetic organisms (ko00710), and several DEGs/DAMs enriched significantly in Ether lipid metabolism (ko00565). DEGs/DAMs of ko00630 enriched significantly under both stress conditions, DEGs/DAMs and DEPs/DAMs of ko00710 enriched significantly under SS and TS, respectively. Therefore, we speculated that plasma membrane responded first to intertidal desiccation and activated stress signal transduction. Organic acids and amino acids involved in osmoregulation were then synthesized and accumulated, meanwhile, energy metabolism was reduced to prevent the accumulation of reactive oxygen species and cellular damage. These pathways worked together to protect blades of P. haitanensis from intertidal desiccation during low tides, which further provided new ideas for breeding cultivars with improved resistance to abiotic stress caused by global warming.