Tetrabutylphosphonium hydroxide (TBPH) aqueous solution, a novel ionic liquid that could dissolve cellulose rapidly at ambient temperature (25 °C), was used for the first time to develop an extraction method for salidroside from Rhodiola crenulata, used as the model sample, with infrared-assisted extraction (IRAE) in this paper. IRAE-TBPH procedures were optimized using a series of single-factor experiments and under optimal conditions, the IRAE-TBPH technique not only took a shorter time (from 1.0 h to 8 min) but also afforded a higher extraction rate of salidroside from the herbs (increased by 15.41–38.65%) compared with other extraction techniques, such as TBPH-based heat reflux extraction (HRE-TBPH), ultrasound-assisted extraction (UAE-TBPH) and conventional solvent (methanol, ethanol and pure water) based IRAE. The results indicated IRAE-TBPH to be a fast and efficient extraction technique. Furthermore, the mechanism of IRAE-TBPH was preliminarily studied by means of the surface structures and chemical compositions of the samples before and after different extraction techniques. On the basis of the destruction of herb surface microstructures, the cellulose dissolving property of TBPH and high efficiency heating of infrared irradiation in the IRAE-TBPH process, the IRAE-TBPH technique eventually achieved the maximum yield value. Therefore, TBPH solution as a novel, effective and alternative solvent with higher extraction efficiency in the IRAE of active compounds from medicinal plants showed a great promising prospect.