As a class of emerging organic contaminants (EOCs), organophosphate flame retardants (OPFRs) have been raising concern due to their persistence, bioaccumulation and toxicity. Therefore, it is urgent need to develop environmental-friendly and high-efficient techniques to remove OPFRs. The degradation kinetics and mechanism of tris-(2-chloroisopropyl) phosphate (TCPP), a representative OPFRs, by UV/TiO2 photocatalytic degradation were explored in current research. It was found that degradation reaction was well documented by first-order kinetics with a k(obs) of 0.3146 min(-1), and hydroxyl radical was identified as a dominating contributor for the TCPP elimination. Simultaneously, six steady intermediate products were generated with the release of Cl- and PO43- as photocatalytic reaction further proceeded. The degradation efficiency can be interfered by natural organic matters, anions and pH value, implying that an incomplete mineralization of TCPP could be ubiquitous in heterogeneous water matrix. Combining the proteomics analysis with KEGG metabolism networks analysis, the process of transmembrane transport and energy generation in Escherichia coli altered by intermediates has proved that the intermediates could be transported and utilized through cellular metabolism. Moreover, the diminution of stress resistance suggested that the toxicity of degradation products through UV/TiO2 photocatalytic degradation was lower than that of intact TCPP. To sum up, environmental safety of degrading intermediate products and the satisfactory detoxification effect of TCPP were identified under appropriate mineralization, indicating that UV/TiO2 photocatalysis technique was safe and high-efficient for TCPP control.