Reaction and distillation separation processes are two significantly energy-intensive unit operations in the chemical industry. Due to the high-temperature reaction and separation conditions, a large amount of waste heat with multiple grades is produced, which should be effectively utilized. In the article, the organic Rankine cycle (ORC) system is adopted to recover the waste heat in the reaction-separation process of cumene synthesis to generate electricity. The design parameters of the ORC system with eight working fluids including R113, R601, R123, R601a, R245ca, R245fa, R600 and R600a are optimized, aiming to maximize annual net economic revenues (NER) through the sequential quadratic programming (SQP). Simultaneously, the thermal efficiency (?ORC) of ORC system with optimal economic performance is calculated for eight working fluids. The results illustrate that R113 performs better than other working fluids in terms of NER and ?ORC. The corresponding annual net electricity generation (NEG), annual NER of ORC system (NERORC) and overall process (NERoverall) and ?ORC can reach 620.83 kW, 0.75 × 105 $/y, 2.11 × 105 $/y and 21.79 %.