Reliability analysis on highly weathered rock slope stability is carried out by means of a combination of first order two moment, Monte-Carlo simulation and finite difference numerical analysis. Firstly, the rock slope is treated as a continuous medium, and the characteristic parameters of the highly weathered rock slope are obtained by using equivalent continuum model. Subsequently, the material parameters of rock slope are defined as two-dimensional variable parameters, and the uncertainty model of the variable parameters is established by employing the first order two moments method. Then the spatial variability of geotechnical parameters is simulated by Monte-Carlo method. Finally, the influence of covariance and autocorrelation distance on safety factor and reliability index is researched by using finite difference method. Results show that the spatial variability of the geotechnical parameters has great influence on the evaluation of specific rock slope stability. The safety assessment for highly weathered rock slope could not be determined by single parameter. As covariance of rock slope parameter increases, the reliability index and safety factor reduce gradually; and with the increase of autocorrelation distance, reliability index increases gradually. Therefore, the effects of spatial variability of geotechnical parameters of rock slope should be considered in conventional slope analysis and design process.