The hydrodynamic cavitation (HC) as an influential advanced oxidation technology is commonly used for treating organic wastewater. In the present research, a CFD model is used to study the hydrodynamic cavitation in multi-hole orifice (MHO). Accordingly, the effect of hole-to-hole interaction in MHO and its influence on the bubble generation and the flow turbulence downstream of the orifice are analyzed. During the cavitation, the central hole exhibits the highest flow rate, i.e., strong jet, over other jets for the dimensionless hole's pitch circle, δ, equal to 50 and 75%. This causes the occurrence of the pitchfork bifurcation phenomenon, and thereby a high level of turbulence intensity behind MHO especially for δ=50%. The value of δ also affects the streamlines curvature at the hole entrance. This curvature influences on the bubble generation due to a reduction in the pressure gradient. The bubble distribution is not uniform at the entrance of each holes because of non-uniform flow separation at the tip holes. The minimum cavitation number and pressure loss are obtained at δ equal to 50%. The MHO thickness, tD=0.5, provides more guidance to the outlet jet and thereby a decrease of the jet's interaction. Also, the results show the significant impact of MHO thickness on the issued jet, which in turn affects the turbulence intensity (i.e., bubble life). Alternatively, increasing the number of holes rather than using larger holes leads to more bubble formation from each hole when the opening area ratio remains constant. Finally, the change in operating conditions of the inlet pressure and the working temperature is studied and the results are discussed.