Neoplasms are one of the main causes of mortality worldwide. Hepatocellular carcinoma (HCC), oesophageal, gastric, and colorectal cancer represent malignancies with major incidence and impact of the gastrointestinal tract. Unfortunately, patients are often diagnosed with advanced stage disease and this is why our aim should be to implement screening and prevention strategies in order to reduce global cancer-related mortality. Human microbiota is defined as a mix of bacteria, eukaryotes, viruses, and archaea that live in our body; these microorganisms interact with immunological, metabolic, endocrinological, and neurological networks contributing to their modulation, through the production of active metabolites. Several studies have shown a correlation between human gastrointestinal (GI) cancers and dysbiosis defined by the qualitative/quantitative alterations of microbiota, but the exact mechanism through which microbiota is able to interfere with our networks and promotes carcinogenesis has not yet been well defined. Nevertheless, we know that H. pylori acts as a risk factor for gastric cancer, while hepatitis viruses C and B represent a trigger for HCC. Following these examples, many researchers hypothesized that gut microbiota may promote GI cancers, through different mechanisms, such as chronic inflammation, promotion of oxidative stress, alterations of immune response and disruption of body homeostasis then pushing cells towards a path of degeneration. In this review, we analysed studies published in 2019 exploring the role that the human microbiota plays in the genesis and progression of GI tract neoplasms. We also explore if and how microbiota interacts with anti-cancer drugs pharmacodynamic and pharmacokinetics during the drug resistance process.