We present a theoretical investigation of the growth orientation dependence of valence‐subband structures in ZnSxSe1−x/ZnyMg1−ySzSe1−zquantum wells grown in the [001], [115], [113], [112], and [111] directions. The results indicate that the in‐plane effective mass of the heavy‐hole subband in the [111]‐oriented structure is substantially smaller than that in the [001] quantum wells. For applications to quantum‐well lasers, the lighter effective mass will lead to a smaller threshold current density, and therefore a better laser performance. Our investigations should provide useful guidelines for the design of II‐VI quantum‐well blue lasers.