Polymer graphitic carbon nitride (g-C3N4) materials have attracted growing interest owing to their impressive applicability in photocatalysis and optoelectronic devices. However, further applications of g-C3N4 materials are greatly restricted by their chemical inertness and insolubility in most solvents. Regarding the rising prospect of g-C3N4 nanosheets in the biomedicalfield, high solubility and biocompatibility are required for the further development of g-C3N4 materials. In this study, a simple one-step thermal polymerization method was designed to prepare fast-soluble mesoporous g-C3N4 nanosheets by using NH4HSO4 as the critical adjuvant. The products, especially the optimal g-C3N4 NSs-4, showed impressive solubility, biocompatibility and partial biodegradability. The enriched surface hydrophilic groups (-NH2 and -OH) may contribute to improving the solubility of g-C3N4 nanosheets, while the partial biodegradability can be ascribed to the presence of the disulfide bond in the g-C3N4 framework. In this system, the NH4HSO4 adjuvant acted not only as O and S sources, but also as a bubbling agent that endows the g-C3N4 a porous structure with greatly enlarged specific surface area and high separation efficiency of photogenerated electron-hole pairs. These integrative positive factors also greatly contributed to the photocatalytic activity of the g-C3N4 nanosheets. This facile, economic and general fabrication strategy for mesoporous, fast-soluble and biocompatible g-C3N4 with superior visible-light photocatalytic activity is promising in environmental, energy and biomedical fields.