Lightweight high-entropy alloys (LHEAs) with body-centered-cubic (BCC) structure have attracted wide attention due to their considerable strength-ductility synergy. However, the lack of work hardening ability is a key weakness, limiting the engineering application. In this study, appropriate contents of rare-earth element yttrium (Y) were added to the as-cast Ti-Zr-V-Nb-Al LHEAs with single BCC structure, and the microstructure and work hardening behavior of these LHEAs were investigated. Benefiting from the addition of Y, these LHEAs generated slight of Y-rich and Y-O-rich phases both in the grains and on the grain boundaries. During plastic deformation, these precipitates can effectively prevent dislocation slip and promote the dislocation intersections and reactions, which can improve the work-hardening ability. Moreover, adding Y can promote the large constitutional supercooling of the LHEAs and refine the grain size of the LHEAs, which also improve the work-hardening ability. Finally, the work hardening of as-cast Ti-Zr-V-Nb-Al LHEAs were successfully turned from negative to positive with 0.2 at% Y addition, with only few ductility loss. Our work provides an effective means of optimizing the mechanical properties, especially the work hardening ability, of as-cast BCC LHEAs.