Non-O1, non-O139 Vibrio cholerae (NOVC) can cause cholera-like diarrhea, but it rarely causes extraintestinal infection, so it is easily overlooked. In this report, we present a case of NOVC detected through blood culture in a 58-year-old male patient with cirrhosis, resulting in severe infection. The patient had been diagnosed with cirrhosis seven years prior and was admitted to the hospital due to abdominal distension and gastrointestinal bleeding. Gram-negative bacilli were isolated from blood cultures and identified as V. cholerae using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and average nucleotide identity (ANI). Moreover, the serum agglutination test showed that the strain was non-O1/non-O139. Further whole genome sequencing and analysis of the strain showed that the strain mainly carried virulence genes tox R, RTX, hly A, T3SS/T6SS, but no resistant genes such as sulII, dfrA1, strB were detected. It provides information for the study of the pathogenic mechanism and drug resistance mechanism of V. cholerae. The patient had severe symptoms and a poor prognosis, indicating that although the NOVC strain infected in this patient had few virulence genes, it was not weak in pathogenicity. It may be caused by the effect of some virulence genes, which should be paid attention to.