The use of phase change materials (PCMs) in building enclosures is an efficient way to reduce the heat gain and/or loss in summer and winter. It was evident that the thermal performance of buildings with PCMs was affected by the outdoor air temperature significantly. However, the influence of humidity, which was serious in the humid subtropical climate was unclear. To explore the effect of PCMs under a humid subtropical climate, the thermal performance of a lightweight building outfitted with PCMs with a melting temperature of 25 °C was investigated. The actual outdoor air temperature with a humidity of 40–90 RH% and wind velocity of 2–6 m/s blowing from the east, west, south, and north was assumed for the performance assessment. A simulated model was developed using EnergyPlus and verified against experimental data. The energy savings by using PCMs was reduced from 3.9% to 2.6% when the outdoor humidity increased from 40 to 90 RH% in summer. However, the savings was not obvious in winter. Annual energy savings decreased from 1.64% to 1.32% with humidity increasing from 40 to 90 RH%. For annual condition, the average energy savings was reduced from 1.43% to 0.92% when the wind speed increased from 2 m/s to 6 m/s. From an economic point of view, the investment payback period was less than 10 years when the PCM price was lower than 18.0 Yuan/kg.