For the heavy pollution and high content of trace soluble heavy metals Cd2+、Cu2+、Zn2+、Ni2+ in waters, a determination method of trace soluble heavy metals in seawater is proposed based on flow injection analysis and spectrophotometry. Firstly, the absorption spectrums of four heavy metal ions are analyzed at different wavelengths. Then, an orthogonal correction set with 4 levels and 4 factors is established as the multiple linear regression analysis model. Finally, the measuring equipment of four heavy metal ions is set up, the concentration of soluble metals Cd2+、Cu2+、Zn2+、 Ni2+ in waters is measured, and the detection limit at 10-9 (ppb) can be achieved.