Chronic exposure to heavy metals has long been recognized as being capable of increasing head and neck cancer (HNC) incidence, such as laryngeal (LC) and nasopharyngeal (NPC), among exposed human populations. The aim of the present study was to evaluate the concentrations of arsenic (As) and cadmium (Cd) in the blood of 145 patients (LC and NPC) and 351 controls in order to establish a potential relationship between these factors and the occurrence of LC and NPC. Mean blood levels of As and Cd in patients (5.67 and 3.51 μg/L, respectively) were significantly higher than those of controls (1.57 and 0.74 μg/L, respectively). The blood levels of As and Cd were mostly significantly higher than those of controls (p < 0.05) after controlling the other risk factors of HNC including tobacco smoking and chewing, and alcohol drinking. Cd levels in blood increase significantly with the number of occupational exposure years for patients (p < 0.05). However, seafood was not found to be contributing as an exposure source. Among these risk factors, smoking (>30 pack years) and occupational exposure (>20 years) presented the most significant association with HNC (OR = 10.22 and 10.38, respectively, p < 0.001). Cd level in blood sample of cases that are occupationally exposed/tobacco users (smokers and chewers) were higher than that of non-occupationally exposed/nontobacco users (p < 0.001). The logistic regression model illustrated that HNC (LC + NPC) was significantly associated with blood levels of As (OR = 2.41, p < 0.001) and Cd (OR = 4.95, p < 0.001).