Salinity in estuaries has an important influence on sediment deposition, delta formation, and fishery economy. The change of runoff in Yellow River (YR), which is the largest river along the Bohai Sea, has an important effect on the salinity of the sea, particularly in Laizhou Bay. In this study, measured runoff data in Lijin hydrological station from 1950 to 2018 are adopted to examine the change of YR runoff into the sea. The study concludes that the runoff of YR is distributed unevenly throughout the year and the amount of runoff mainly concentrates during the flood season. Results show a decreasing trend at a significant level of α = 0.95, with a range of −6.17 × 10 9 m 3 yr −1. Three groups of runoff are set by using the Finite-Volume Coastal Ocean Model numerical model to analyze the change of salinity in Laizhou Bay. These modeled effects were compared with water level observations made by Bayuquan, Tanggu, and Penglai gauge stations and salinity surveys conducted by Longkou gauge station. Model results and observations of salinity distributions and coastal water level showed good agreement. We can conclude that the distribution of salinity in Laizhou Bay is high in the east and low in the west. Furthermore, it responded quickly to the change of the runoff from YR. Under conditions of high river discharge, the low-salinity zone increased in horizontal direction and reached the bottom in vertical direction.