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An inverse association may exist between cancers and neurodegenerative diseases, although convenient biomarkers for verifying this inverse association are lacking. Plasma neurofilament light chain (NfL) is a novel biomarker for neurodegenerative diseases, such as Alzheimer’s disease (AD), but it has not been measured in patients with cancers, such as gastric cancer (GC). We aimed to explore whether plasma NfL could be a biomarker for GC and AD and whether an inverse association of NfL exists between GC and AD. In this study, plasma NfL levels of 60 normal controls (NC), 91 GC subjects, and 74 AD subjects were measured by a highly sensitive single-molecule array assay. We found that GC subjects expressed lower plasma NfL levels but AD subjects expressed higher plasma NfL levels than NCs. After controlling for confounding factors, plasma NfL levels in the GC group were associated with serum tumor marker levels, and plasma NfL levels in the AD group were associated with cognitive performance and cerebrospinal fluid (CSF) pathological marker levels. Across the entire cohort, plasma NfL levels were associated with cognitive performance, CSF pathological marker levels and serum tumor marker levels. These results suggest thatplasma NfL may be a potential biomarker for GC and AD and may be convenient for evaluating the inverse association between cancers and neurodegenerative diseases.