The containment spray system (CSS) has a significant role in limiting the risk of radioactive exposure to the environment. In this work, the optimal droplet size and pH value of spray water to prevent the fission product release have been evaluated to improve the performance of the spray system during in-vessel release phase. A semikinetic model has been developed and implemented in MATLAB. The sensitivity and removal rate of airborne isotopes with the spray system have been simulated versus the spray activation and failure time, droplet size, and pH value. The alkaline (Na 2 S 2 O 3 ) spray solution and spray water with pH 9.5 have similar scrubbing properties for iodine. However, the removal rate from the CSS has been found to be an approximately inverse square of droplet diameter (1/ 2 ) for Na 2 S 2 O 3 and higher pH of spray water. The numerical results showed that 450 m-850 m droplet with 9.5 pH and higher or the alkaline (Na 2 S 2 O 3 ) solution with 0.2 m 3 /s-0.35 m 3 /s flow rate is optimal for effective scrubbing of in-containment fission products. The proposed model has been validated with TOSQAN experimental data.