The purpose of this study was to evaluate the effect of self-etching primer on glass-ceramic at different reaction durations. Fifty specimens of lithium disilicate ceramic were divided into five groups based on the surface treatment (n = 10); Group A (control): no treatment, Group B: treated with 5%-hydrofluoric acid (HF) followed by a primer, Group C: treated with one-bottle system self-etching primer; (Monobond Etch & Prime (MEP)) for 20 s plus 40 s reaction time, Group D: MEP for 20 s plus 80 s reaction time, Group E: MEP for 20 s plus 120 s reaction time. The outcomes of shear bond strength (SBS), failure mode and surface topography were assessed. Statistical analyses were performed using ANOVA, Chi-squared test and Tukey's test at a significance level of alpha = 0.05. The control group (A) demonstrated the lowest SBS value (0.11MPa, SD:0.022) which was statistically significant, compared to other groups (P < 0.0001). However, the mean SBS values were not statistically significant among the other four experimental groups. Group B yielded the highest SBS value (13.79MPa, SD:3.57), although was not statistically significant when compared to group C (11.60MPa, SD:1.23), group D (11.94MPa, SD:1.24), and group E (11.67MPa, SD:0.64), P > 0.05. Scanning electron microscope (SEM) showed increased surface roughness in HF/primer specimens compared to MEP. Stereomicroscopy analyses showed that the main mode of failure was adhesive failure in group A, while was mixed failure in the other experimental groups, with no statistical significance between the groups. The self-etching system can be considered as an alternative for the glass-ceramic surface treatment without compromising the bond strength. The time required for conditioning seems to be sufficient with 40 seconds reaction time.