Microwave-assisted solid-phase synthesis method was simple, convenient, and fast, and herein adopted to produce nitrogen-doping carbon dots (N-CDs) in only 3 min. The N-CDs possessed high fluorescence quantum yield up to 15.9% with satisfactory stability to the environmental pH, ionic strength, and ultraviolet radiation. Particularly, the N-CDs had excellent dispersibility in both water and water-compatible organic solvents with similar fluorescence properties. Sunitinib, a small-molecule tyrosine inhibitor effective for some solid tumors, was found to quench the fluorescence of N-CDs in these media via the inner-filter effect. Hence, it was convenient to combine the proper sample pretreatment with the N-CD probe for sensing sunitinib avoiding the medium incompatibility problem. For rat plasma sample, salting-out liquid-liquid extraction was employed to minimize the sample matrix and concentrate the target sunitinib from aqueous to acetonitrile. The fluorescence detection of sunitinib was then achieved in acetonitrile by the addition of the proper amount of N-CDs. The method provided a good linearity of 0.1 mu g/mL to 7 mu g/mL with a limit of detection of 30 ng/mL, which met the requirement of the therapeutic drug monitoring of sunitinib. The developed method was potential for on-site detection of sunitinib.