Many proteins secreted from plant cells into the surrounding extracellular space help maintain cell structure and regulate stress responses in the external environment. In this study, under Pi replete and deplete conditions, 652 high-confidence secreted proteins were quantified from wild type (WT) and OsPHR2-overexpressing suspension-cultured cells (SCCs). These pro-teins were functionally grouped as phosphatases, signal transduction proteins, patho-gen-related (PR) proteins, cell wall remodeling proteins and reactive oxygen species (ROS) metabolism proteins. Although phosphate response (PHR) transcription factors regulate two-thirds of Pi-responsive genes at the transcriptional level, only 30.6% of the Pi-starvation-regulated secretory proteins showed significant changes in OsPHR2 overex-pressing SCCs. The OsPHR2-dependent systemic Pi signaling pathway mainly regulates phosphatases and pathogen-related proteins, which are involved in the utilization of organ-ophosphate, pathogen resistance, and rhizosphere microorganisms’ colonization. The OsPHR2-independent local Pi signaling pathway, on the other hand, largely regulated ROS metabolism proteins, cell wall remodeling proteins, and signal transduction proteins, which are involved in modifying cell wall structure and root architecture. The functions of differ-entially expressed secretory proteins between WT and OsPHR2 overexpressing plants under Pi-sufficient and Pi-deficient conditions were further confirmed by analysis of the acid phosphatase activity, ROS content, and cell wall composition.