A spray-drying assisted solid-state method to prepare spherical layer-structured H2TiO3 ion sieve (LSTIS) particles is reported herein. The effects of synthesis parameters (calcination temperature, calcination time, and the lithium-titanium molar ratio) on adsorption–desorption performance (the delithiation ratio, titanium dissolution loss, and the adsorption capacity) were investigated. The as-prepared LSTIS exhibited an equilibrium adsorption capacity of 30.08 mg·g−1 (average of 25.85 mg·g−1 over 5 cycles) and ultra-low titanium dissolution loss of less than 0.12% (average of 0.086% over 5 cycles). The LSTIS showed excellent selectivity toward Li+ in Na+, K+, Mg2+, and Ca2+ coexisting saline solutions where its adsorption capacity reached 27.45 mg·g−1 and the separation factors of Li+ over the coexisting cations exceeded 100. The data suggests that the LSTIS is promising to competitively enrich Li+ from saline solutions.