Karst caves in Wuhan are featured with shallow buried depth, small height, and high-head groundwater. Through numerical orthogonal test by MIDAS GTS, the significance of five major factors affecting the safe distance between the tunnel of Wuhan metro line 27 and the hidden karst caves is examined. The five major factors involve surrounding rock level, lateral pressure coefficient, span of cave, ratio of height to span of cave, and permeability coefficient. Results suggest that surrounding rock level and span of cave have significant impact on the safe distance between tunnel and cave whether the peripheral cave is located below, lateral to or above the tunnel, while permeability coefficient has no significant effect. Lateral pressure coefficient has a significant effect only when the peripheral cave is located beneath the tunnel. The ratio of height to span of cave has a significant influence only when the peripheral cave is located lateral to the tunnel. In association with nonlinear multiple regression analysis on the results, formulas for estimating the safe distance between tunnel and cave when caves are located below, lateral to and above tunnel are obtained. Case study proves that the proposed formulas are reliable.