As bimodal magnetic-fluorescent imaging agents, the preparation of ZnS:Tb,Gd and ZnS:Er,Yb,Gd nanoparticles via a facile homogeneous precipitation method is reported. The results show that these nanoparticles are almost spherical in shape with a diameter of 100–200 nm approximately and a major phase of wurtzite-structured ZnS. The products can successfully label the human hepatocellular carcinoma (HepG2) cells and present low toxicity even at concentrations up to 5 mg mL−1. Additionally, for the ZnS:Er,Yb,Gd nanoparticles calcinated above 950 °C, NIR-to-visible up-conversion fluorescence were obtained, which is believed to be superior to traditional ZnS-based bioimaging agents with down conversion. In MRI studies, they reveal a longitudinal relaxivity rate (r1) of 39.46 mM−1 s−1 and 57.8 mM−1 s−1, respectively, which are much larger than the conventional Gd-DTPA and currently reported Gd-base nanoparticles, suggesting great potential as MRI agents.