The objective of this study was to assess the control on formation of formaldehyde (FA) during the heating processing in jumbo squid by compound inhibitors. The substances inhibiting the formation of FA were selected in the squid, and the property of inhibitors to reduce FA was analyzed. The compound inhibitors was optimized by single factor experiment and orthogonal experiment. The results showed that the amount of FA decreaed significantly in the squid treated by citric acid (CA), CaCl₂, MgCl₂, tea polyphenolic (TP), mulberry flavonoids (MF), whereas, it increased greatly treated by Na₂SO₃, Fe²⁺ in presence of the reductants of cysteine and ascorbate. The low concentration of inhibitors, CA, CaCl₂ and TP, could reduce more than 90% of the amount of FA in supernatant of squid, and the optimal inhibiting concentrations were 10 mmol/L, 10 mmol/L and 0.1%, respectively. The thermal decomposition of trimethylamineN-oxide (TMAO) to FA, dimethylamine (DMA) and trimethylamine (TMA) was significantly inhibited by CA, CaCl₂, MgCl₂, while, the amount of FA could be reacted effectively by TP and MP in the squid at high temperature. Then the amount of FA and DMA dropped significantly, and the content of protein was not affected for the squid slice treated by the optimal compound inhibitors, 0.04% TP and 10 mmol/L CaCl₂. Therefore, the compound inhibitors of FA have a potential application in the control of the amount of FA in squid processing.