**1. Introduction**

Cancer is a generic term for a broad group of diseases caused by dysregulation of cell growth and exacerbated cellular proliferation. Contrary to the orderly and self-regulating manner of normal cells in the human organism, cancer cells divide and colonize tissues usually reserved for other cells. Cancer incidence is caused by many factors, such as unhealthy diet and poor physical activity, excessive alcohol intake, exposure to oncogenic viruses (e.g., human papillomavirus; HPV), immoderate sun exposure, tobacco consumption, among others [1]. Cancers with the highest mortality globally are lung cancer (18.2%), colorectal cancer (9.5%), liver cancer (8.4%), stomach cancer (7.8%), and breast cancer (6.9%) [2].

Lung cancer (LC) is a complex type of cancer that remains the leading cause of death worldwide. By 2021, an estimated 235,760 persons will be diagnosed with LC, whereas 131,880 persons will probably die of LC [3]. The incidence of LC is subjected to exposure to physical and chemical components, family history, genetic alterations, and comorbidities. Considering that the estimated survival rate of LC is five years, several modifications have been made to diagnostic tools and treatment schemes to improve a patient's prognosis. The histological analysis and molecular scanning of LC lead to its categorization into small-cell lung cancer (SCLC, 15% of all lung cancers) and non-small cell lung cancer (NSCLC, 85% of all lung cancers) [4].

NSCLC is one of the two major categories of LC; its subtypes include adenocarcinoma, large-cell carcinoma, and squamous cell carcinoma. Over the past decades, there has been an increasing understanding of the biology, diagnosis, and treatment of NSCLC. Nowadays, it is known that the incidence of NSCLC is related to family history, genetic susceptibility, and exposure to physical and chemical carcinogens. NSCLC is diagnosed by testing genetic mutations, imaging techniques, and histologic features. This type of cancer is treated with various medical and pharmacological approaches, such as surgery, radiotherapy, targeted therapy, and immunotherapy [5].

The treatment of NSCLC presents diverse limitations, such as drug cytotoxicity, incompatible pharmacokinetic profiles, low accumulation rate in tumor tissues, side effects, and poor solubility. Therefore, the study of relatively new therapeutic molecules with anticancer potential such as flavonoids has unveiled promising results to treat NSCLC *in vitro* and *in vivo*.

Flavonoids are one of the largest classes of secondary metabolites produced in plants and foods. Flavonoids are classified into various subclasses, such as anthocyanins, flavones, flavonols, and flavanones. Despite their ecophysiological relevance, multiple studies have assessed many flavonoids' anticancer properties and synergistic action [6]. However, the anti-NSCLC properties of some flavonoids persist elusively.

We consulted PubMed, Google Scholar, and SciFinder to compile contemporary literature about flavonoids' distribution, chemical features, and therapeutic properties. In addition, this work is focused on the chemical characteristics, sources, biosynthesis, pharmacokinetics, anticancer, and anti-NSCLC activities of four selected flavonoids: luteolin, naringenin, kaempferol, and baicalein. A general scenario of LC and NSCLC is also addressed. In the literature, the four selected flavonoids have been reported to interfere with metastatic processes, arrest the cell cycle, restrain oncogenic signaling pathways activation, inhibit the invasion of NSCLC, improve the efficacy of current chemotherapy drugs, and diminish NSCLC cells' proliferation *in vitro* and *in vivo*. Further studies are required to extend our knowledge about the anti-NSCLC properties, efficacy, safety, and toxicity of luteolin, naringenin, kaempferol, and baicalein.
