Gastric neuroendocrine carcinoma (GNEC) is rare cancer detected in the stomach. Previously, we demonstrated that the poorer prognosis of GNEC patients compared with gastric adenocarcinoma (GAC) patients was probably due to the lack of response to chemotherapy. Thus, it is crucial to study the specific GNEC gene expression pattern and investigate chemoresistance mechanism of GNEC. The transcriptome of GNEC patients was compared with that of GAC patients using RNA-seq. The KEGG analysis was employed to explore the specific differential expression gene function enrichment pattern. In addition, the transcriptomes of two GNEC cell lines, ECC10 and ECC12, were also compared with those of two GAC cell lines, MGC-803 and AGS, using RNA-seq. Comparing patient samples and cell lines transcriptome data, we try to uncover the potential targets and pathways which may affect the chemoresistance of GNEC. By combing all transcriptome data, we identified 22 key genes that were specifically up-regulated in GNEC. This panel of genes probably involves in the chemoresistance of GNEC. From our current experimental data, NeuroD1, one of the 22 genes, is associated with the prognosis of GNEC patients. Knockdown of NeuroD1 enhanced the sensitivity to irinotecan of GNEC cell lines. Our research sheds light in identifying a panel of novel therapeutic target specifically for GNEC clinical treatment which has not been reported before.