In this paper we study the Szeged index of partial cubes and hence generalize the result proved by V. Chepoi and S. Klav\v{z}ar, who calculated this index for benzenoid systems. It is proved that the problem of calculating the Szeged index of a partial cube can be reduced to the problem of calculating the Szeged indices of weighted quotient graphs with respect to a partition coarser than \(\Theta\)-partition. Similar (but more general) result was recently proved by S. Klav\v{z}ar and M. J. Nadjafi-Arani. Furthermore, we show that such quotient graphs of partial cubes are again partial cubes. Since the results can be used to efficiently calculate the Wiener index and the Szeged index for specific families of chemical graphs, we consider \(C_4C_8\) systems and show that the two indices of these graphs can be computed in linear time.