This study aimed to develop a new type of low-salt and healthy compound salt agent for pickled tilapia (Oreochromis sp.) fillets processing technology. In this paper, the effects of different additions of sodium chloride and potassium chloride, sodium malate and white sugar on the sensory evaluation, salt content, water content, proteolysis index and texture of marinated tilapia fillets were investigated by single factor experiment with fresh tilapia fillets respectively, and optimization of mixing parameters of compound salt agent by Box-Behnken Response Surface method. Results indicated the effect of potassium chloride, sodium malate, sodium chloride on the quality of tilapia fillets was significant. The best processing technology of compound salt agent pickled tilapia fillets were as follows: the addition of potassium chloride was 2.67%, sodium malate was 1.32%, sodium chloride was 9.1%, white sugar was 0.5%. Under these conditions, the actual sensory evaluation was 89, the actual salt content was 2.81%, and the relative error of the target prediction value was 2.39%, indicating that the experimental model could be used to predict the actual value. Preliminary results indicate that compared with the control group, the sodium content of tilapia fillets decreased by 22.92%, which provided a new fast pickling processing technology of low salt and low sodium for the processing of tilapia.