Background: Cashmere goat is famous for its high-quality fibers. The growth of cashmere in secondary hair follicles exhibits a seasonal pattern arising from circannual changes in the natural photoperiod. Although several studies have compared and analyzed the differences in gene expression between different cashmere growth stages, the selection of samples in these studies relies on research experience or morphological evidence. Distinguishing cashmere growth cycles according to gene expression patterns may help to explore the regulation mechanisms related to cashmere growth and the effect of melatonin from a molecular level more accurately. Results: In this study, we applied RNA-sequencing to the hair follicles of three normal and three melatonin-treated Inner Mongolian cashmere goats sampled every month during a whole cashmere growth cycle. A total of 3559 and 988 genes were subjected as seasonal changing genes (SCGs) in the control and treated groups, respectively. The SCGs in the normal group are divided into three clusters, and their specific expression patterns help to group the cashmere growth cycle into anagen, catagen and telogen stages. Some canonical pathways such as Wnt, TGF-beta and Hippo signaling pathways are detected as promoting the cashmere growth, while Cell adhesion molecules (CAMs), Cytokine-cytokine receptor interaction, Jak-STAT, Fc epsilon RI, NOD-like receptor, Rap1, PI3K-Akt, cAMP, NF-kappa B and many immune-related pathways are detected in the catagen and telogen stages. The PI3K-Akt signaling, ECM-receptor interaction and Focal adhesion are found in the transition stage between telogen to anagen, which may serve as candidate biomarkers for telogen-anagen regeneration. Pairwise comparisons between the control and melatonin-treated groups also indicate 941 monthly differentially expressed genes (monthly DEGs). These monthly DEGs are mainly distributed from April and September, which reveal a potential signal pathway map regulating the anagen stage triggered by melatonin. Enrichment analysis shows that Wnt, Hedgehog, ECM, Chemokines and NF-kappa B signaling pathways may be involved in the regulation of non-quiescence and secondary shedding under the influence of melatonin. Conclusions: Our study decodes the key regulators of the whole cashmere growth cycle, laying the foundation for the control of cashmere growth and improvement of cashmere yield.