Organic room-temperature phosphorescence (RTP) materials have demonstrated great potential applications in optoelectronics, anticounterfeiting, and biomedicine fields. Among them, the RTP properties of host-guest systems can be easily regulated by changing their component parameters, which has attracted widespread attention. However, the key factor of the hosts (crystalline or noncovalent interaction network) for boosting phosphorescence emission at room temperature was still unclear. Herein, a triphenyl phosphor in the estradiol system was heated to remove the crystal water and then cooled to turn it into a powder. This enabled the afterglow brightness to improve by more than 90-fold and the phosphorescent quantum yield by over 700-fold. Further studies have indicated that the hydrogen bonding interactions of estradiol's -OH group were tuned during these processes, from bonding with crystal water to bonding with guests and then constructing a strong network with the guests. The triplet excitons thus were effectively stabilized, which, coupled with the suitable T