Slopes stabilised with piles are seldom analysed considering uncertainties in the parameters of the pile-slope system. Reliability analysis of the pile-slope system quantifies the degree of uncertainties and evaluates the safety of the system. In the present study, the reliability analysis of a slope stabilised with piles is performed using the first-order reliability method (FORM) based on Hasofer-Lind approach. The implicit performance function associated with the factor of safety (FS) of the slope is approximated using the response surface method with multiple linear regression. The design matrices used for the multiple linear regression are based on both the 2k factorial design augmented with a centre run (2k fact-centred design) and face-centered cube design (FCD). The deterministic analyses are performed using three-dimensional finite element method for the generation of response data for the design matrix. The order of the polynomial model used to approximate the performance function is decided based on suitable hypothesis tests on regression coefficients as well as the assessment of the model summary statistics. Results are compared with the results of the Monte Carlo simulation. It is observed that the optimum location of the row of piles is at the middle of the slope to achieve the maximum FS. The results show that the reliability of the system is not uniform for different pile configurations, even if the system deterministically satisfies the target factor of safety (FSt) criterion. The FSt should be selected judiciously as it is observed that the reliability of the system changes drastically with the FSt level. The results of the 2k fact-centred design and FCD are in good agreement with each other. The procedure of the FCD is computationally costly and hence the use of 2k fact-centred design is recommended, provided the response of the system is sufficiently linear over the factorial space. The calibration of load and resistance factors is performed using FORM for the limit state of global stability. These reliability-based load and resistance factors ensure a target reliability index for the pile-slope system.