As one of the popular slope protection structure of inland waterway, the interlock concrete block revetment is well known by its advantages of water and earth preserving, energy saving, and environmental protection. Research on the stability of interlocking concrete block during operation period is important for the design, construction and maintenance of revetment. Based on the project of Jining section of the Grand Canal from Beijing to Hangzhou, the stability of interlock concrete block under different operation conditions and impacts of ship waves were simulated and analyzed by numerical modeling. Results indicated that: (1) Thickness of the block was the primary parameter among all the design parameters. As the thickness values increasing, the index of stability would increase accordingly. (2) Angle between the wave curve and the water line at the shore was an important parameter in determining ship waves. (3) The main damaged area of the interlock concrete was below the static water, which could be calculated according to navigation conditions of the canal. (4) The opening ratio of the block would not affect the stability index obviously. Therefore the value of opening ratio could be determined in terms of construction convenience and vegetation coverage.