Patients with advanced gastric cancer (Gc) have a poor prognosis with a median overall survival of 10-12 months. long non-coding rna nicotinamide nucleotide transhydrogenase-antisense rna1 (nnT-aS1) and sex-determining region Y-related high mobility group box 4 (SoX4) have been reported to be associated with the progression of various types of cancer; however, the regulatory mechanism between nnT-aS1 and SoX4 in Gc is not completely understood. reverse transcription-quantitative Pcr was used to detect the expression levels of nnT-aS1, microrna (mir)-142-5p and SoX4. Western blotting was performed to assess the protein expression levels of SoX4, β-catenin, c-Myc, Bcl-2 and e-cadherin. The proliferation, apoptosis, migration and invasion of GC cells were determined using MTT, flow cytometry and Transwell assays. The relationship between mir-142-5p and nnT-aS1 or SoX4 was investigated using a dual-luciferase reporter assay. nnT-aS1 and SoX4 were upregulated, whereas mir-142-5p was downregulated in Gc tissues and cells compared with normal tissues and cells. Both nnT-aS1 and SoX4 knockdown inhibited Gc cell proliferation, migration and invasion, and enhanced Gc cell apoptosis. Moreover, the results indicated that nnT-aS1 modulated SoX4 expression by sponging mir-142-5p. in addition, SoX4 overexpression reversed nnT-aS1 knockdown-mediated effects on Gc cell proliferation, apoptosis, migration and invasion. nnT-aS1 knockdown blocked the Wnt/β-catenin signaling pathway via the mir-142-5p/SoX4 axis. collectively, the present study indicated that nnT-aS1 knockdown decreased Gc cell proliferation, migration and invasion, and induced Gc cell apoptosis by regulating the mir-142-5p/SoX4/Wnt/β-catenin signaling pathway axis.