ABSTRACT: As the only regenerative organ of mammals, antler could grow rapidly without carcinogenesis. To understand the molecular mechanisms of the growth of sika deer antler, we used de novo RNA-seq analyses to determine the differential expression of unigenes and miRNAs from antler at 15, 60, 90, and 110-day. A total of 55004 unigenes, 208 known miRNAs and 38 novel miRNAs were identified. 10182 unigenes and 35 miRNAs were differentially expressed between 60-day and 15-day antler, 13258 unigenes and 53 miRNAs were differentially expressed between 90-day and 60-day antler, and 10740 unigenes and 27 miRNAs were differentially expressed between 110-day and 90-day antler. GO and KEGG analyses showed that DE unigenes and miRNA were mainly related to chondrogenesis, osteogenesis and inhibition of oncogenesis, that were closely associate with antler growth. We also constructed mRNA-mRNA and miRNA-mRNA interaction networks related to chondrogenesis, osteogenesis and inhibition of oncogenesis of antler. The results showed that mRNA (COL2A1, SOX9, WWP2, FGFR1, SPARC, LOX etc.) and miRNAs (miR-145, miR-199a-3p, miR-140, miR-199a-5p etc.) may play important roles in chondrogenesis and osteogenesis of antler, and mRNA (TP53, Tpm3 and ATP1A1 etc.) and miRNAs (miR-106a, miR-145, miR-1260b and miR-2898 etc.) may have key roles in inhibiting the carcinogenesis of antlers. In this study, we identified miRNAs and unigenes related to chondrogenesis, osteogenesis and inhibition of oncogenesis of antler. This will provide a reference for in-depth analysis of the molecular mechanism of antler growth without carcinogenesis, and also provide valuable information for cartilage- and bone-related disease treatment, cancer treatment.