This study compared the effects of hot air drying (HAD) and vacuum drying (VD) on the physicochemical qualities of lily (Lilium lancifolium Thunb.) bulbs. The results showed that VD treatment effectively reduced the browning of lily scales with a total color difference (ΔE) 42–73% lower than those of HAD group. Two drying treatments enhanced the total phenolic content (TPC) of the lily bulbs effectively. TPC increased with rising drying temperatures, and under isothermal conditions, the TPC of VD group was 1.1–1.6-fold higher than that of HAD group. Five typical phenolic compounds were identified in lily bulbs. As the predominant phenolic fraction, regaloside A of VD group was 51–291% above HAD group. Regaloside B was temperature sensitive and would be destroyed by high temperature. In parallel, VD treatment elevated the antioxidant activity overall, which could be contributed by phenolics and some Maillard reaction products. Furthermore, drying significantly improved the antiproliferative activity of lily bulbs, with samples treated with 120 °C HAD and 60 °C VD exhibiting the strongest antiproliferative capacity. The present investigation demonstrated that VD treatment effectively improved the physicochemical quality of lily bulbs and would provide a theoretical basis for optimizing drying conditions to obtain higher-quality lily bulbs.