Effective urban square ventilation is important for the living comfortand health of residents. This research aims to establish some principles of street entry layouts for urban square ventilation optimization. Using computational fluid dynamics (CFD) simulation techniques, two types of street entry squares (two-intersection and four-intersection) were investigated under the effect of surrounding buildings. Three indices—the spatial mean velocity (<V*>), air change rate (ACH) and mean flow rates (<Q>) through the street entry and square roof—were calculated to quantify the square ventilation performance. The simulation results indicate that the surrounding buildings could influence the square space ventilation. When the surrounding building conditions change to a building coverage ratio of 0.25, the <Q> entering through the street entry can be reduced by 35%, and the <V*> within the square decreases by more than 45%. The optimal street entry layout design depends greatly on the wind direction. When the wind direction is perpendicular to the square street entry, the corner oblique-entry layout square shows a better ventilation performance than the other designs. When the wind direction is oblique to the square street entry, the <V*> declines greatly (up to 68%), and the lateral-entry layout design shows the best ventilation performance.