In this study, several heat-integrated distillation processes are compared to separate the close-boiling cyclo-hexanone (CHON)-cyclohexanol (CHXA) for improving energy efficiency. A 4-column scheme, including two light ends columns in DRP (distillation with recycle process), a CHON column and a CHXA column, is introduced as the prototype scheme. To make improvement, light and heavy split DRP are compared for energy optimization upon the prototype. The light split DRP turns out to be superior and thus used for subsequent steps. Four heat-integrated schemes including double-effect distillation (DED), heat pump assisted distillation (HPAD), DED plus HPAD (DEHP) and double HPAD (DHPAD) are sequentially suggested and evaluated based on total annualized cost (TAC). The results show TAC reductions from the prototype of 32.2%, 23.6%, 29.2% and 10.8% for DED, HPAD, DEHP and DHPAD, respectively. The DED scheme requires the lowest TAC due to the 48.4% operating cost and 8% capital cost saving, whereas the DEHP scheme has the lowest 56.3% operating cost reduction with 11.1% more capital investment. The line of thinking in this work will benefit in other close-boiling systems for higher energetic efficiency and economic profit.