In our previous study, polyurethane (PU) based multilayer films assembled with weak polyelectrolytes exhibited controllable loading and release properties, but would be decomposed in high salt solution. Herein, a strong polyelectrolyte, poly(styrene sulfonic acid) sodium (PSS), was introduced to fabricate multilayer films. The salt tolerance of the film was investigated by evaluating the loading and release profiles towards model drug in salt solution with different concentrations. Results showed that the release behavior of the film, as well as its loading capacity, can be tuned by varying the salt concentrations. And the film showed a good salt tolerance that can remain integrity even after 6 cycles of drug loading and release in 600 mmol·L−1 NaCl solution. It showed that the salt tolerance of PU based films can be greatly improved through assembling with strong polyelectrolyte.