Past earthquakes like the Mexico City earthquake of 1985 have highlighted the effect of soft soils on the seismic response of structures. Several researchers have concluded that the consideration of soil-structure interaction is essential. Most studies on reinforced concrete (RC) buildings considering SSI, carried out in the past, have not considered the soil material uncertainty. It is worth mentioning that soil properties contain a certain level of uncertainty that can influence the RC frame’s response under the influence of SSI. The present work focuses on quantifying the effect of soil material uncertainty on the response of RC frame building. A planar mid-rise RC moment frame, designed as per Indian standard codes, has been considered and modelled in OpenSees. The numerical model of the frame along with soil is analyzed using the direct approach by considering the nonlinear behavior of both soil and structure. The uncertainty in the soil properties is considered in terms of Cohesion, Unit weight, Poisson's ratio, and Shear modulus, with the coefficient of variation (COV) as 10%. Further, 50 samples of material properties are generated assuming lognormal distribution which are combined using the Latin-Hypercube sampling (LHS) method to maintain the equal probability. A total of 1200 numerical analyses are performed, considering 24 ground motion records. Peak inter-story drift ratio (PISDR) and peak roof displacement (PRD) are the considered engineering demand parameters (EDPs) and a statistical study has been performed to understand the effect of soil material uncertainty on the seismic response of the RC frame.