The purpose of the study is to investigate the effects of brine salting and high-pressure processing (HPP) on the microbial inactivation and quality parameters of mackerel fillets. Mackerel fillets were immersed in 3% and 9% sodium chloride brine for 90 min at refrigerator temperature, and then treated at 300, 400, 500, and 600 MPa pressure for 5 min. The microbial counts and physicochemical qualities of the fish were examined. In comparison with fish fillets treated with brine or high pressure alone, those treated with the combination of brine salting and HPP showed significantly reduced aerobic plate count (APC) and psychrotrophic bacteria count (PBC). The hardness and chewiness of salt-brined fillets were obviously lower than those of the unsalted fillets under the same pressure condition. Thus, brine salting imparted mackerel fillets a softer texture, which compensated for the HPP-induced increased hardness and chewiness of the fillets. The L* (lightness) and ΔE (colour difference) values of the fillets increased with increasing pressure, with or without brine salting. Conversely, a* (redness) values decreased with increasing pressure. The samples treated with 3% brine in combination with 300 or 400 MPa pressure had a* values similar to those of the samples processed under similar HPP conditions alone but showed lower ΔE values than the other groups. Therefore, as a very high pressure would adversely affect the texture and colour of the fish fillets, this study suggests that immersion in an appropriate brine concentration (3%) and treatment with HPP at 400 MPa for 5 min improved or maintained the colour and texture relatively well and produced a synergistic bactericidal effect.