Hot water mound drench treatment has broad application prospects in the control of the red imported fire ant (RIFA), Solenopsis invicta Buren (Hymenoptera: Formicidae). However, much work still needs to be carried out to provide a theoretical basis and technical support for the use of this method against RIFAs under field conditions. In this study, we monitored the temperature changes at different depths within RIFA nests during laboratory-simulated hot water mound drench experiments and evaluated the lethal effect of hot water treatment on RIFAs. Furthermore, the targeted removal effect of hot water mound drench treatment on RIFA nests under field conditions was evaluated. Results indicated that the temperature at depths of 5, 15, and 25 cm inside the simulated ant nests was higher than 51.1 °C within 30 min after treatment, resulting in a 100% mortality rate for RIFAs at all tested depths. Under field conditions, when nests were disturbed, the percentage of RIFAs crawling out of their nests gradually increased with time after disturbance, reached its maximum value at 25 or 30 s after the disturbance, and then gradually decreased. Single hot water mound drench treatment (each ant nest was treated with 17.8–21.6 liter of hot water at a temperature of 97–100 °C) can significantly reduce the RIFA population in ant nests and lead to a 72.7% reduction in the number of surviving ant nests. However, the safety, operability, and timelines of hot water mound drench treatment for RIFA field control still need further investigation.