In this study, CoFe2O4-TiO2 was prepared by hydrothermal method, in which CoFe2O4 was the core and TiO2 was the shell, and HA@CoFe2O4-TiO2 was obtained by hyaluronic acid modification. The physicochemical properties of the nanocomposites were characterized by scanning electron microscopy (SEM) imaging, energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), ultraviolet-visible absorption spectroscopy (UV-Vis) and Fourier transform infrared spectroscopy (FTIR). CCK-8 method was used to investigate the toxicity of HA@CoFe2O4-TiO2 nanocomposites on HL60 cells in dark chamber, and the inactivation effect of photodymanic therapy (PDT). The mechanism of interaction between CoFe2O4, hyaluronic acid and TiO2 on PDT inactivation of HL60 cells was preliminarily investigated by fluorescence spectra (FS), intracellular ROS production and uptake level analysis of nanocomposites. The experimental results showed that the morphology of HA@CoFe2O4-TiO2 was regular and spherical, and the size met the requirements of cell uptake. The visible response range of TiO2 was broadened with CoFe2O4. Dark toxicity experiment proved that HA@CoFe2O4-TiO2 nanocomposites were less toxic to HL60 cells under darkroom conditions. Meanwhile, Compared with the groups treated with TiO2 and CoFe2O4-TiO2 nanoparticles, the photocatalytic inactivation efficiency of the group treated with HA@CoFe2O4-TiO2 was as high as 82.6%. Therefore, it has the potential to become a photosensitizer for the PDT treatment of leukemia in vitro, improving photodynamic efficiency and targeting.