The rapid development of sonodynamic therapy (SDT) provides a promising strategy for treating deep-seated multidrug-resistant (MDR) bacterial infection. However, the extreme scarcity of biologically functional and highly efficient sonosensitizers severely limits the further clinical practice of SDT. Herein, the lattice-strain-rich Ti3C2 (LS-Ti3C2) with greatly improved sonosensitizing effect is one-step synthesized using Ti3C2 and meso-tetra(4-carboxyphenyl)porphine (TCPP) by the solvothermal method for realizing extraordinary SDT. The intervention of TCPP causes all the Ti–O chemical bonds and most of the Ti–F chemical bonds on the surface layer of Ti3C2 to break down. The amino groups of TCPP are then recombined with these exposed Ti atoms to perturb the order of the Ti atoms, resulting in displacement of the Ti atoms and final lattice structural distortion of Ti3C2. The inherent lattice strain narrows the band gap of Ti3C2, which mainly facilitates the electron–hole pair separation and electron transfer under ultrasound irradiation, thereby resulting in US-mediated reactive oxygen species (ROS) production and the subsequent robust bactericidal capability (99.77 ± 0.16%) against methicillin-resistant Staphylococcus aureus (MRSA). Overall, this research offers a perspective into the development of Ti-familial sonosensitizers toward SDT practice.