In this article, we present a chemoaffinity-mediated synthetic strategy toward trivalent rare earth (RE) sulfides-based nanocrystals with poor affinity between cation and anion (i.e., RE3+ and S2-). With the affinity mediation among multiple constituents based on hard and soft acid and base theory, we synthesized a series of monodisperse NaRES2 nanocrystals (RE = La to Lu, Y). The revelation of the nanocrystal growth mechanism from both experimental evidence and crystal structure modeling has enabled a robust control over the sizes and morphologies of the nanocrystals. This principle of chemoaffinity has also promised the synthesis of well-defined but even more complex RE-based hetero-nanostructures (i.e. NaLaS2-Au, Au@NaLaS2, NaLaS2@Ag2S, Au@NaLaS2(MAg2S) with tunable optical properties. Furthermore, this synthetic method has yielded durable NaCeS2-based red nano-pigments under ambient conditions, with superior brightness and permeability in polydimethylsiloxane.