The S block is a low-middle porosity and low-middle permeability reservoir. This paper studied the operation parameters for steam flooding with the combination of vertical and horizontal wells by numerical simulation. The result shows that the optimum operation parameters are as following: the vertical distance is 15 m between the vertical well and horizontal well, and the vertical distance is 7 m between the horizontal well and reservoir bottom; after eight cycles of vertical well and six cycles of horizontal well, formation pressure dropped down to 5 MPa; the best steam injection rate is 84 m3/d, downhole steam dryness is greater than 40%, and production-injection ratio is 1.2. These optimum operation parameters make the steam flooding effective in S block, enhance the oil recovery factor, also provide reliable theoretical basis of operation parameters for steam flooding with the combination of vertical and horizontal wells in other similar reservoirs, and have very good reference significance.