Protein pKa is a fundamental physicochemical parameter that dictates protein structure and function. However, accurately determining protein site-pKa values remains a substantial challenge, both experimentally and theoretically. In this study, we introduce a physical organic approach, leveraging a protein structural and physical-organic-parameter-based representation (P-SPOC), to develop a rapid and intuitive model for protein pKa prediction. Our P-SPOC model achieves state-of-the-art predictive accuracy, with a mean absolute error (MAE) of 0.33 pKa units. Furthermore, we have incorporated advanced protein structure prediction models, like AlphaFold2, to approximate structures for proteins lacking three-dimensional representations, which enhances the applicability of our model in the context of structure-undetermined protein research. To promote broader accessibility within the research community, an online prediction interface was also established at isyn.luoszgroup.com.