The Japanese spineless cuttlefish (Sepiella japonica) is an important economic species and animal model. Many studies suggested that microRNAs (miRNAs) play an important regulatory role in the embryonic development process. However, comparative miRNA profiles during embryogenesis of cuttlefish have not been reported before. In this study, miRNA profiles were obtained from embryos of S. japonica from eye primordium formation to larval growing stage by miRNA sequencing. A total of 1528 known miRNA and 203 novel miRNAs were identified during different development stages. Among which, 62 differentially expressed miRNAs (DEMs) among different development stages were identified. GO analysis indicated that the potential target genes for these DEMs were involved in many GO terms including intracellular membrane-bounded organelle, cell morphogenesis, regulation of developmental process, ant etc. In addition, miRNA-mRNA network analysis indicated that many of target genes of these DEMs were involved in integral component of membrane. In conclusion, our work provided a global view of miRNA expression profiles during embryonic development of S. japonica.