Tsunami-tide interactions in the Seto Inland Sea (SIS) were investigated by taking into account the effects of tidal currents on the tsunami propagation in terms of the arrival time and the run-up heights along the coast of SIS. The initial tsunami wave profile was introduced by the possible Tokai-Tonankai-Nankai Earthquake of the magnitude Mw9.0, which is equivalent to that of 2011 Tohoku Earthquake. Numerical experiments with four different tidal phases, flood, ebb, high, and low, reveal that the water depth changes due to tides affect the tsunami propagation in terms of heights and arrival time. During high tides, the tsunami propagates faster and reaches higher than during the low tides. In addition, during the flood tides with rising water level, tsunami propagates faster than during the ebb tides. Further investigation also shows that the tsunami-tide interaction changes the tsunami signal such that the tsunami-only spectra shifts the spectral peaks after considering the tsunami-tide interactions. Local oscillation modes characterized by local bathymetry and topography shift to higher frequency modes due to the non-linear tsunami-tide interaction. To reduce the uncertainties involved in tsunami predictions and coastal defenses and management, it is strongly recommended to simulate tsunamis together with tides in shallow water environments.