Two-dimensional (2D) metal–organic framework (MOF) nanosheets have emerged as a new member of 2D nanomaterials for molecular sieving, energy conversion and storage, catalysis and biomedicine. In this paper, a highly dense assembly of porphyrin achievable in porphyrin-integrated MOF nanosheets induced by an ionic liquid is obtained by sonication exfoliation of its bulk crystals. The 2D layered structure MOF, [BMI]₂[Ca₃(H₂TCPP)₂(μ₂-OH₂)₂(H₂O)₂] (1), was firstly prepared by using the ionic liquid assisted synthetic method (H₆TCPP = meso-tetra(carboxyphenyl) porphyrin, BMI = 1-butyl-3-methylimidazolium). The laminated layers in 1 clearly indicate a weak interlayer non-covalent interaction but a strong metal–carboxylate bonding within the layers, which facilitates the exfoliation of 1 to form 2D MOF nanosheets (1 NSs). Powder X-ray diffraction (PXRD), high-resolution transmission electron microscopy (HR-TEM) and fast Fourier transform (FFT) patterns revealed that 1 NSs could maintain their crystalline structure after exfoliation. These MOF nanosheets exhibited excellent aqueous dispersibility, biodegradability and high cytotoxicity under light irradiation against MCF-7 cells.