The technology of three-chamber regenerative thermal oxidation with negative pressure ventilation and waste heat recovery was introduced. Based on a case study in package printing industry with treatment of volatile organic exhaust gas, a detailed description of the composition and operation method of this system was given. The mass concentration of volatile organic compounds (VOCs) was continuously measured on line with gas chromatograph. The results show that the daily average of inlet VOCs concentration is 800～1 800 mg/m³, and the daily average of outlet VOCs mass concentration is 7.96～28.89 mg/m³, which means a removal efficiency within 97.8%～99.3%. The daily peak of inlet VOCs mass concentration fluctuates between 2 216.79～3 968.44 mg/m³, with a fluctuation of outlet VOCs peak concentration within 2.4～72.34 mg/m³, and the removal efficiency is 97.8%～99.9%. The operating energy consumption is low, and the recovered waste heat can completely meet the heating demand of the printing process, which leads to good energy saving effect. Finally, the key points to be noticed in engineering application were pointed out.