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The Asian citrus psyllid (ACP), <i>Diaphorina citri</i> Kuwayama (Hemiptera: Liviidae), is an important transmission vector of the citrus greening disease C<i>andidatus</i> Liberibacter asiaticus (<i>C</i>Las). The <i>D. citri</i> midgut exhibits an important tissue barrier against <i>C</i>Las infection. However, the molecular mechanism of the midgut response to <i>C</i>Las infection has not been comprehensively elucidated. In this study, we identified 778 differentially expressed genes (DEGs) in the midgut upon CLas infection, by comparative transcriptome analyses, including 499 upregulated DEGs and 279 downregulated DEGs. Functional annotation analysis showed that these DEGs were associated with ubiquitination, the immune response, the ribosome, endocytosis, the cytoskeleton and insecticide resistance. KEGG enrichment analysis revealed that most of the DEGs were primarily involved in endocytosis and the ribosome. A total of fourteen DEG functions were further validated by reverse transcription quantitative PCR (RT-qPCR). This study will contribute to our understanding of the molecular interaction between CLas and D. citri.