In this study, an efficient and magnetically recoverable catalyst consisting of 6-methylguanamine supported on CoFe2O4 nanoparticles for the preparation of isoxazol-5(4H)-one derivatives has been synthesized. Different physicochemical methods such as Fourier transform infrared (FT-IR), X-ray powder diffraction (XRD), and field emission scanning electron microscopy (FE-SEM) were used to characterize the obtained catalyst. The nanocatalyst reusability was investigated by using five consecutive reaction runs. The present procedure possesses some merits such as mild reaction conditions, excellent yields, short reaction time, avoidance of using organic solvents, and easy workup.