Guided-mode resonance (GMR) displays a wide range of optical properties that could prove useful for many applications in photonics. We report the enhancement of laser emission from the GMR sparse grating-based dye laser. The enhancement is due to an introduction of the low-refractive-index (low-n) separation layer, which causes a strong interaction between the local electric field and dye molecules. Finite-difference time-domain method is used to study how the structure’s geometry, including the thickness of the separation layer and the fill factor of the grating, affects the electric field and laser intensity. The results show that the emission can be enhanced by a factor of up to 8 compared with high-refractive-index SU-8 as the separation layer. The laser intensity reaches to the maximum value when the fill factor of the grating is 0.2, i.e., the sparse grating is used. The threshold of the low-n GMR dye laser is also examined. This design can effectively improve the performance of pumped photonic band-edge lasers.