It is a common type of tunnel under-cross the roadbed slope with weak inter-layer. Rainfall infiltration will cause soil softening, matric suction and strength reduction, which seriously threaten the safety of slope and tunnel. This paper presents a case where a tunnel underlying the roadbed slope with weak inter-layer in Guiyang 1# line, China. The seepage calculation model in MIDAS GTS/NX software, considering hydraulic permeability coefficient characteristic curve and soil-water characteristic curve, was used to analyze the stress and deformation of the roadbed slope and tunnel. The results reveal that rainfall infiltration has great influence on the deformation of roadbed slope with weak inter-layer and the force of internal tunnel. Slope displacement increases rapidly in the early stage and decreases in the late stage, but the absolute value of displacement increases continuously and the slope safety factor decreases gradually, which makes the slope in a dangerous state. The force of tunnel lining increases in the early stage and decreases with the recovery of soil strength after rainfall. The control effects of anchor cable and anti-slide pile reinforcement on slope sliding and tunnel stress were studied. And the anchor cable reinforcement measure is more effective on reducing slope slip and tunnel lining structure internal force.