In x Ga 1 - x As y Sb 1 - y epilayers with a fixed In content of x = 0.145 were grown on GaSb(100) substrates using liquid-phase epitaxy (LPE). The lattice mismatch between the quaternary epilayers and substrates was analyzed for different As contents ( y ) by X-ray ω -2 θ . Epilayers with As content between y = 0.120 and y = 0.124 exhibited a positive lattice mismatch, leading to compressive strain. These samples showed a high crystalline quality and flat surfaces, as confirmed by high-resolution X-ray diffraction (HR-XRD) and atomic force microscopy (AFM). Quaternary alloys with As content between y = 0.133 and y = 0.141 displayed a negative lattice mismatch, resulting in tensile strain. Structural defects in these samples were evidenced by HR-XRD and on AFM micrographs. Raman measurements also revealed that lateral strain has a direct impact on the intensities of the LO-like, phonon–plasmon and disorder-activated longitudinal acoustic modes. For all In x Ga 1 - x As y Sb 1 - y films, photoluminescence (PL) spectra showed a bound exciton (BE) transition, with additional features observed in samples under tensile strain, indicating the involvement of native defect centers and donor–acceptor pairs. This study provides new insights into the effect of lateral strain on the crystalline and surface quality, and optical properties of quaternary alloys, relevant for novel optoelectronic applications.