Aneuploidy is usually more detrimental than altered ploidy of the entire set of chromosomes. To explore the regulatory mechanism of gene expression in aneuploidy, we analyzed the transcriptome sequencing data of metafemaleDrosophila. The results showed that most genes on the X chromosome undergo dosage compensation, while the genes on the autosomal chromosomes mainly present inverse dosage effects. Furthermore, long noncoding RNAs (lncRNAs) have been identified as key regulators of gene expression, and they are more sensitive to dosage changes than mRNAs. We analyzed differentially expressed mRNAs (DEGs) and differentially expressed lncRNAs (DELs) in metafemaleDrosophilaand performed functional enrichment analyses of DEGs and the target genes of DELs, and we found that they are involved in several important biological processes. By constructing lncRNA-mRNA interaction networks and calculating the maximal clique centrality (MCC) value of each node in the network, we also identified two key candidate lncRNAs (CR43940 and CR42765), and two of their target genes,Sin3AandMED1, were identified as inverse dosage modulators. These results suggest that lncRNAs play an important role in the regulation of genomic imbalances. This study may deepen the understanding of the gene expression regulatory mechanisms in aneuploidy from the perspective of lncRNAs.