Fluorinated human serum albumin conjugates were prepared and tested as potential metal-free probes for ¹⁹F magnetic resonance imaging (MRI). Each protein molecule was modified by several fluorine-containing compounds via the N-substituted natural acylating reagent homocysteine thiolactone. Albumin conjugates retain the protein’s physical and biological properties, such as its 3D dimensional structure, aggregation ability, good solubility, proteolysis efficiency, biocompatibility, and low cytotoxicity. A dual-labeled with cyanine 7 fluorescence dye and fluorine reporter group albumin were synthesized for simultaneous fluorescence imaging and ¹⁹F MRI. The preliminary in vitro studies show the prospects of albumin carriers for multimodal imaging.