Historical events are expected to affect population genetic differentiation and DNA molecular evolution, but the impact of these effects remains a matter of debate. Here, for Conandron ramondioides (Gesneriaceae), we analyzed the genetic structure and phylogeographical pattern of 248 individuals from 13 populations, distributed in mainland China and Taiwan Island, based on the nucleotide sequence and haplotype of the coding sequence of CYCLOIDEA1 (GCYC1). Among the populations, we found a high level of haplotype diversity (h = 0.831) and a relatively low level of nucleotide diversity (D ij = 0.004). Both the haplotype network and the neighbor-joining tree constructed from GCYC1 haplotypes suggest two major geographical groupings, one on the mainland and the other on Taiwan. Consistently, AMOVA analysis revealed high genetic differentiation between these groupings, with 84.65% variation partitioning the two regions, and the two groupings shared no haplotype. On the mainland, population genetic differentiation was correlated with more recent events, presumably Pleistocene glaciations and human activities since the Neolithic. In addition, C. ramondioides GCYC1 rapidly accumulated neutral mutations, consistent with this gene being silenced or down-regulated in actinomorphic lineages of the Lamiales, such as Conandron.