Abstract: Salmon bone soup was prepared by ultrasonic-assisted heating, and the cooking process was optimized by response surface test using soluble proteins, sensory score, and amino acid nitrogen as the indicators. Furthermore, the taste characteristics difference between fish bone soups obtained by ultrasonic-assisted heating and traditional heating was investigated by electronic tongue, amino acid automatic analyzer and high performance liquid chromatography. The results showed that the optimum conditions of salmon bone soup prepared by ultrasonic-assisted heating were as follows: Ratio of material to water 1:2 g/mL, ultrasonic time 96 min, and ultrasonic power 800 W. The soluble protein, amino nitrogen, and sensory score of fish bone soup boiled under the above conditions were 192.30 mg/mL, 0.036 g/100 mL, and 8.43, respectively, which was close to the predicted value of the model. Compared with the fishbone soup prepared by the traditional heating process, the ultrasonic-assisted heating facilitated the intensity of umami, richness, and salty taste, decreased the intensity of sourness, and increased the content of taste nucleotides and umami amino acids. In conclusion, ultrasonic-assisted cooking can improve the overall taste characteristics of salmon bone soup and enhance the flavor quality.