Nitrogen (N), phosphorus (P), and potassium (K) are important for plant growth and development. MicroRNAs (miRNAs) play important roles in regulating plant response to nutrient (N, P, and K) deficiencies. Several miRNAs have been identified under nutrient deficiency conditions in many plant species. However, the manner in which miRNAs regulate the interaction between NPK signaling pathways under multiple nutrient deficiency remains largely unknown. We systematically compared and identified microRNAs involved in both single and triple NPK nutrient deficiency responses. We identified 32 shoot and 17 root miRNAs differentially expressed under potassium deficiency. Several NP starvation-associated miRNAs including miR169s and miR399s, were also regulated by K deficiency. Several identified miRNAs including miR5565c, miR5564, and miR1432 have not previously been associated with respectively N, P, and K deficiency (?N, ?P, and ?K). Expression correlation analysis between miRNAs and their predicted targets showed that miR169, miR172, and miR160 displayed expression trends exactly opposite to those of their corresponding predicted targets. Of 550 predicted novel miRNAs, novel_mir_42 was upregulated in shoots under?K but was downregulated under?N and ?P. The effects of combined NPK starvation were not a simple addition of the individual stresses on sorghum seedlings. The identified common and specific differen-tially expressed miRNAs were observed under single and combined NPK deficiencies. These findings will help to further elucidate the functions of microRNAs and their interactions under multiple nutrient deficiency.