Nitrogen is an essential nutrient element for maize (Zea mays L.) growth and development, yield, and grain quality formation. To explore the key genes and reveal the physiological and molecular mechanisms in maize kernels under low nitrogen stress, in this study, the contents of amino acids and amino acid derivatives, as well as transcriptome sequencing of B73 kernel at six days after pollination (6 DAP) were analyzed under both low nitrogen and sufficient nitrogen treatments. The results showed that: under low nitrogen stress, the contents of 10 amino acids or amino acid derivatives were increased, of which the contents of threonine, β-amino-isobutyric acid, histidine, β-alanine, and lysine were increased the most, with the increase ranged from 71.1 to 153.1 %; however, the contents of other 21 amino acids or amino acid derivatives were decreased, of which the contents of ornithine, cystine, asparagine, phenylalanine, and α-aminobutyric acid were decreased the most, with the decrease varied from 51.6 to 65.8 %. Transcriptomic analysis showed that compared with sufficient nitrogen treatment, the 3 185 and 2 612 significantly up-regulated and down-regulated differentially expressed genes (DEGs) were identified in maize kernel under low nitrogen stress, respectively; GO enrichment analysis showed that these DEGs were mainly enriched in cellular processes, metabolic processes, biological regulation, and stimulus responses; KEGG analysis showed that these DEGs were mainly enriched in cell signal, biological cycle rhythm regulation, as well as biosynthesis and metabolic pathways. In addition, a total of 12, 9, 20, 10, and 21 DEGs/differentially expressed transcription factors were further detected in the nitrogen metabolism pathway, cyanoamino acid metabolism pathway, as well as AP2/ERF-ERF, bZIP, and WRKY transcription factor families, respectively. Therefore, these candidate genes may be important gene resources for maize kernels response to low nitrogen stress, which may lay the foundation for the molecular mechanism of maize response to low nitrogen stress and develop low nitrogen tolerance maize varieties.