Shisen-Sho is a tile-based one-player game. The instance is a set of 136 tiles embedded on 8×17 rectangular grids. Two tiles can be removed if they are labeled by the same number and if they are adjacent or can be connected with at most three orthogonal line segments. Here, line segments must not cross tiles. The aim of the game is to remove all of the 136 tiles. In this paper, we consider the generalized version of Shisen-Sho, which uses an arbitrary number of tiles embedded on rectangular grids. It is shown that deciding whether the player can remove all of the tiles is NP-complete.