Non-uniform blast injection often occurs in blast furnace (BFs) ironmaking process, but the consequences in the inner state remain unclear under industrial operating conditions. This paper presents a numerical study of three-dimensional (3D) flow and thermochemical behaviors inside a 5000-m3 commercial BF under non-uniform blast injection. This is based on a recently developed computational fluid dynamics (CFD) process model. The model has been validated under experimental and industrial conditions. It is used here to study the effects of tuyere closure on the asymmetric distributions of 3D inner state and the overall performance of the BF. The numerical results show that the increase in inactive tuyere number substantially enlarges the deadman size and shifts the highest deadman boundary from the BF center to the periphery, consistent with the lab-scale experimental observations. Also, the tuyere closure causes significantly asymmetric distributions of gas, solid, and liquid velocities and temperature, as well as reactions. The phenomenon occurs mainly in the low part of the BF and is more pronounced at a larger inactive tuyere number. When the inactive tuyere number is large, a "W"-shaped cohesive zone (CZ) is observed over the inactive tuyeres, the same as observed by a low-temperature hot-experimental BF model. Corresponding to this "W"-shaped CZ, a cavity forms in the CZ, beneath which a strong liquid flow develops, causing the substantial non-uniformity in liquid temperature distribution. Additionally, tuyere closure affects carbon consumption and liquid temperature oppositely in the regions over the active and inactive tuyeres. These effects are canceled out by each other, leading to inconsiderable variations of overall performance indicators like top gas utilization factor and liquid temperature.