Abstract: Exploring the path of industrial development under the constraint of ecological safety is an crucial prerequisite for regional industrial cooperation and an essential topic in constructing a modern ecological economic system and achieving high-quality development. This study takes the "Six Counties" in the Yangtze River Delta Industrial Cooperation Zone (YDICZ) as a case study and employs the coupling coordination degree and gray Markov models to analyze the relationship between ecological safety and industrial development, as well as their influencing factors, from 2015 to 2022. Additionally, this study predicts the development trend of coupling coordination from 2023 to 2030. The results indicate that: (1) the ecological safety index and industrial development index in the "Six Counties" region both increased from 2015 to 2022. In 2022, the ecological safety index exceeded the industrial development index in all counties (cities) except Changxing County. (2) The coupling coordination degree between ecological safety and industrial development showed a stable upward trend from 2015 to 2022, with the highest in Anji County (0.760) and the lowest in Langxi County (0.661). (3) Air quality, pollutant emissions, and industrial structure were identified as the main obstacles to improving the coupling coordination degree (D) between industrial development and ecological safety in the "Six Counties" region. Specifically, the average annual concentration of fine particulate matter (PM_2.5), the intensity of sulfur dioxide emissions, the proportion of primary industry in GDP, and the proportion of eco-tourism revenues in the total output value of the service industry have the most significant impacts on this coupling coordination degree (D). (4) Predictions suggest that by 2030, the coupled coordination degree (D) of ecological safety and industrial development of all the six counties (cities) will reach a high level of coordination, with the lowest value in Langxi County (0.983). These findings provide a valuable basis for promoting the comprehensive shaping of an eco-friendly industrial layout and realizing higher quality integrated development in the YDICZ, and offer references for the development of county-level industry in similar regions.