A novel and efficient protocol for the oxidation of β-isophorone (β-IP) using molecular oxygen without any additives catalyzed by 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) has been established. The generally accepted catalytic mechanism of alcohols by the oxoammonium cation (TEMPO+) derived from TEMPO indeed fails to explain our experimental observations, because a favorable radical-based process is confirmed by electron spin resonance measurements. Our results show that a plateau of the time-dependence curve is observed in the oxidation of β-IP with TEMPO at low temperature, which is quite different from that of N-hydroxyphthalimide (NHPI). The proposed mechanism of this catalytic process is also compared with that of NHPI. The theoretically characterized reaction pathways show that unlike the phthalimide N-oxyl radical, TEMPO promotes the oxidation via its interaction with the active intermediate hydroperoxide (ROOH) rather than its initial interaction with β-IP, and byproduct water also assists the α-H atom transfer from ROOH to TEMPO. In addition to the intensive oxidation of alcohols catalyzed by TEMPO, the present study widens its specific applications in the active C–H bonds of hydrocarbons, and also provides new insights into its promoted metal-free oxidation.