Refractory high-entropy alloys (RHEAs) composed of Ti, Zr, Hf, and Nb have emerged as promising materials for high-temperature aerospace applications due to their exceptional balance of strength and toughness, coupled with a reduced density and softening resistance. This study delves into the influence of alloy composition on the mechanical properties, a pivotal aspect in the design of RHEAs. We investigate a series of Ti48-xZrxHf26Nb26 (x = 14, 18, 22, 26, 30, 34) alloys, prepared through suction casting and homogenization treatments. The phases, microstructure, and fracture morphology of these alloys are analyzed using X-ray diffraction (XRD), scanning electron microscopy (SEM), and electron backscattered diffraction (EBSD), subsequent tensile tests provide insights into the strength and elongation characteristics of alloys. The homogenized alloys consistently exhibit one BCC phase with equiaxed grains, whereas the fracture mode shifts from intergranular to transgranular, and return to intergranular as the Zr content increases. Experimental results reveal an asymmetry mechanical behavior, alloys with higher Ti content display superior toughness (elongation 17.83 % for Ti = 34 at%) compared to those with higher Zr content (elongation 16.05 % for Zr = 34 at%). Among them, the Ti22Zr26Hf26Nb26 alloy achieves the peak tensile strength of 695.25 MPa, indicating an inverse relationship between strength and toughness. Solid-solution strengthening and chemical short-range orderings emerge as the predominant contributors to the overall strength of the TiZrHfNb alloys. To gain a deeper understanding of the mechanical behavior at the atomic scale, we performed first-principles calculations to investigate the elastic properties and charge density of Ti48-xZrxHf26Nb26 alloys in the BCC structure. These calculations shed light on the underlying mechanisms governing the strength and toughness behavior. The present work offers valuable insights into the design of mechanical properties of TiZrHfNb RHEAs, serving as a paradigm for future materials development in this field.