The glass-forming ability (GFA) of Ti-Zr-Be ternary alloys is dramatically improved by partially replacing Be with Ni. Centimeter-scale fully amorphous samples can be obtained in a wide Ni content range of 4 at. % ~ 12 at. %. In particular, some of the developed Ti-Zr-Be-Ni alloys exhibit a critical diameter up to 20 mm, which is larger than that of other quaternary Ti-based bulk metallic glasses (BMGs). Moreover, Ni addition also enhances the yield strength and compressive plastic strain of Ti-Zr-Be alloys obviously. Based on the experimental results, the effect of substituting elements addition on the glass-forming ability of Ti-Zr-Be alloys has been systematically investigated and an empirical composition design method for the development of novel Ti-based BMGs with large GFA has been proposed.