Cadmium (Cd) stress is a cost-effective, clean, and environmentally friendly approach for microalgal lipid production and wastewater treatment. To study the regulatory networks involved in the growth and development of microalgae, the relationship between calcium and reactive oxygen species (ROS) signalling in the regulation of cell growth and lipid biosynthesis and Cd biosorption after Cd treatment were analysed. The highest lipid content (52.78%) and productivity (96.75 mg L-l d(-1)) were enhanced by 1.59- and 1.39-fold in algal cells treated with 80 mu M and 40 mu M Cd, respectively, compared to the control. The protein content, ROS, antioxidases, Ca2+ and lipid biosynthetic gene transcription levels were upregulated by Cd induction. Additionally, the results indicated that increased endogenous Ca2+ could alleviate oxidative stress by activating antioxidases and mediating Cd biosorption, resulting in cell growth modulation and lipid accumulation. These results demonstrated that Cd stress is a useful strategy for lipid production and Cd bioaccumulation in micro algae and that there is vital interaction between ROS and Ca2+ levels in the regulation of lipid accumulation under Cd stress.