In the current work, the influences of 12% X (X = Ti, V and Ti+V) on the structure and mechanical properties for AlCrFeNi matrix are compared in parallel. After mixing different component, parent phases (NiAl + Cr-Fe) of (AlCrFeNi)88%X12% multi-principal element alloys (MPEAs) can't result in phases separation. Nevertheless, 12 at% Ti- and V-mixed MPEAs lead to extra strengthening through new precipitating phases of L21 (Ni2TiAl) and BCC (Fe-V). For (AlCrFeNi)88%Ti6%V6%, the two precipitating phases promote the synergistic strengthening of the strength and compressive strain. Ti is more effective than V in enhancing grain boundary energy of matrix, because Ti can induce more negative enthalpy of mixing, which makes the aggregation easier. Following identical mixing content, V causes pronounced solid solution strengthening but does not benefit the grain boundary strengthening, triggering an increase in ultimate strength of AlCrFeNi88%V12%. Significantly, the effectiveness of coordination strengthening is boosted by mixing 6%Ti+ 6%V. (AlCrFeNi)88%Ti6%V6% has excellent compressive yield strength and strain, which is 1403.4 MPa and 23.1%, respectively. Our present analysis suggests that strengthening mechanism is applicable to explain the differences in nano interstitial structure, low Ti diffusion and non-equilibrium pinning effect of cooperative reinforcement of BCC (Fe-V) and L21(Ni2TiAl) phases.