Esophageal squamous cell carcinoma (ESCC) accounts for about 90% of global esophageal cancers, with high incidence in Eastern and Central Asia, parts of Africa, and South Africa. Risk factors include tobacco, alcohol, polycyclic aromatic hydrocarbons, high-temperature foods, diet, and oral health. While tobacco and alcohol are linked to ESCC in some regions, other factors are more significant in others. Genetic and environmental factors contribute to ESCC susceptibility, but research is limited, especially in Asia and Africa. ESCC is more common in men, but this ratio varies by region. Incidence trends show decreases in Western countries but not in high-risk areas. ESCC is associated with various risk factors, including betel quid, pickled vegetables, poor oral health, and microbiome changes. Diet, particularly fruits and vegetables, may reduce ESCC risk, but evidence is limited. Alcohol and tobacco are major risk factors, with interactions between them increasing ESCC risk. PAHs, found in food and cooking, are also linked to ESCC. Genetic factors, such as mutations in the RHBDF2 gene, increase ESCC risk. Genome-wide association studies have identified several genetic regions associated with ESCC, but further research is needed. ESCC remains a major cause of cancer death globally, with limited research infrastructure in high-risk areas. Future studies are needed to better understand ESCC etiology and improve prevention strategies.Esophageal squamous cell carcinoma (ESCC) accounts for about 90% of global esophageal cancers, with high incidence in Eastern and Central Asia, parts of Africa, and South Africa. Risk factors include tobacco, alcohol, polycyclic aromatic hydrocarbons, high-temperature foods, diet, and oral health. While tobacco and alcohol are linked to ESCC in some regions, other factors are more significant in others. Genetic and environmental factors contribute to ESCC susceptibility, but research is limited, especially in Asia and Africa. ESCC is more common in men, but this ratio varies by region. Incidence trends show decreases in Western countries but not in high-risk areas. ESCC is associated with various risk factors, including betel quid, pickled vegetables, poor oral health, and microbiome changes. Diet, particularly fruits and vegetables, may reduce ESCC risk, but evidence is limited. Alcohol and tobacco are major risk factors, with interactions between them increasing ESCC risk. PAHs, found in food and cooking, are also linked to ESCC. Genetic factors, such as mutations in the RHBDF2 gene, increase ESCC risk. Genome-wide association studies have identified several genetic regions associated with ESCC, but further research is needed. ESCC remains a major cause of cancer death globally, with limited research infrastructure in high-risk areas. Future studies are needed to better understand ESCC etiology and improve prevention strategies.