A HPLC method was developed for the simultaneous analysis and determination of sulfamethazine and p-hydroxybenzoic acid in solution. The results showed that when acetonitrile-phosphoric acid aqueous solution (pH = 3.15) was used as the mobile phase and the volume ratio was 18∶82, sulfamethazine and p-hydroxybenzoic acid were quickly separated in 9 minutes. The RSD values of precision and stability of the method are less than 2%. The average recoveries of sulfamethazine and p-hydroxybenzoic acid are 98.73% and 98.90%, respectively. On this basis, the sulfamethazine-p-hydroxybenzoic acid cocrystal was prepared by the solution method. At 298.15K and 303.15K, the ternary phase diagram of the cocrystal in acetonitrile solvent was established. The XRD, DSC, and SEM were used to characterize the sulfamethazine and p-hydroxybenzoic acid and the partially dried solid phase at 298.15K. The results show that the phase diagram of the sulfamethazine-p-hydroxybenzoic acid-acetonitrile system is a symmetrical phase diagram. As the temperature increases, the sulfamethazine-p-hydroxybenzoic acid cocrystal region increases, which is conducive to the formation of the cocrystal .