Entamoeba histolytica is a human pathogen, responsible for amoebic dysentery and invasive extraintestinal disease. The parasite faces several types of stress within the host, and to establish a successful infection it must generate a robust adaptive response against host defense mechanisms. In order to obtain comprehensive information of gene expression changes in E. histolytica under growth stress, we have (1) optimized the proteomics protocol to increase the protein coverage in E. histolytica, and (2) integrated proteomic data with transcriptomic analysis under the same conditions. We have applied this approach to better understand the cellular response during serum-starvation. Label-free quantitative proteomics was performed, and compared with mRNA levels based on RNA-seq data to decipher regulation at translational and transcriptional levels. Across all samples, 2344 proteins were identified, which is an improvement over the maximum recorded number in E. histolytica proteomic studies so far. A total of 127 proteins were found to be differentially expressed and associated with functions including antioxidant activity, cytoskeleton, translation, catalysis, and transport, which revealed proteomic signatures to distinguish serum-starved from normal trophozoites. Gal/GalNAc-inhibitable lectin, Lgls, Hgl3 and Igl were repeatedly identified as significantly altered in serum-stress condition. Further, integration of transcriptomic and proteomic data revealed instances of post-transcriptional regulation. Six highly expressed transcripts had low corresponding protein expression, indicating translational repression. Conversely, eleven transcripts showed much greater downregulation compared with their corresponding proteins, indicating translational induction, or increased stability of these proteins during serum stress in E. histolytica. This multi-omics approach enables more refined gene expression analysis that would not be possible at the mRNA or protein levels alone. Our study provides important data to further understand the adaptive response of E. histolytica to growth stress.