Cycas panzhihuaensis L. Zhou&S. Y. Yang (Cycadaceae) is an endangered gymnosperm species endemic to the dry-hot valley of the Jinsha River basin in southwest China. Although the wild C. panzhihuaensis population from Panzhihua Cycad Natural Reserve is well protected and its genetic diversity has been well assessed, the genetic characteristics of populations outside the nature reserve, which face larger risks of extinction, remain unknown. Furthermore, the population genetics and historical dynamics of this endemic and endangered species have not been examined across its entire range. In this study, to analyze the genetic diversity, phylogeographical structure and demographic history of C. panzhihuaensis from all its seven known locations, we sequenced and compared molecular data from chloroplastic DNA (psbA-H, psbM-D, and S-G), single-copy nuclear genes (PHYP, AC5, HSP70, and AAT) from 61 individuals, as well as 11 nuclear microsatellite loci (SSR) from 102 individuals. We found relatively high genetic diversity within populations and high genetic differentiation among populations of C. panzhihuaensis, which is consistent with the patts of other Asian inland cycads. Although no sig-nificant phylogeographical structure was detected, we found that small and unprotected populations possess higher genetic diversity and more unique haplotypes, which revises our understanding of di-versity within this species and deserves due attention. Analysis of demographic dynamics suggest that human activity might be the key threat to C. panzhihuaensis. Based on the genetic characterization of C. panzhihuaensis, we propose several practical guidelines for the conservation of this species, especially for the populations with small sizes.