With this study, the design and tuning of multi-loop for multivariable (2x2) CSTR will be made in order to achieve optimum CSTR control performance. This study used Bequette model reactor and MATLAB software and is expected to be able to cope with disturbances in the reactor so that the reactor system is able to stabilize quickly despite the distractions. In this study, the design will be made using multi-loop approach, along with PI controller as the next step. Then, BLT and auto-tune tuning method will be used in PI controller and given disturbances to both of tuning method. The controller performances are then compared. Results of the study are then analyzed for discussions and conclusions. Results from this study have shown that in terms of disturbance rejection, BLT is better than auto-tune based on comparison between both of controller performances. For IAE for the case of temperature, BLT is 30% better than auto-tune, but it is almost the same for the case of concentration. For settling time for the case of concentration, BLT is 30% better than auto-tune, and for the case of temperature, BLT is 18% better than auto-tune. For rise time for the case of concentration and temperature, BLT is 30% better than auto-tune.