Electrostatic effect is a primary mechanism for nanofiltration (NF) in rejecting mineral ions in water. In this study, efforts were devoted to understand the change of membrane surface charges by pH-titrating synthesized poly(piperazine-amide) material in the presence of NaCl or CaCl2 of different concentrations. It revealed that the membrane surface charges were resulted from dissociation and protonation of functional groups when in contact with NaCl solution, and additionally from specific complexation of calcium ions by acidic groups when in contact with CaCl2 solution. Viewing the membrane with a uniform surface potential could not well explain the rejection behavior for CaCl2-containing solutions. We proposed to treat the membrane surface as a mixed collection of positively and negatively charged regions, with these regions able to reject ions relatively separately. Increasing calcium ion concentration in the feed water could increase the proportion of positively charged regions. The enhanced shielding on positively-charged regions could reduce the rejection of calcium ions while that on negatively-charged regions could increase the rejection. This study could act to initiate further studies on the roles and importance of the coexistence of negative and positive charges at membrane surface in electrostatic effect on salt rejection.