C50 carotenoids, as unique bioactive molecules, have many biological properties, including antioxidant, anticancer, and antibacterial activity, and have a wide range of potential uses in the food, cosmetic, and biomedical industries. The majority of C50 carotenoids are produced by the sterile fermentation of halophilic archaea. This study aims to look at more cost-effective and manageable ways of producing C50 carotenoids. The basic medium, carbon source supplementation, and optimal culture conditions for Halorubrum sp. HRM-150 C50 carotenoids production by open fermentation were examined in this work. The results indicated that Halorubrum sp. HRM-150 grown in natural brine medium grew faster than artificial brine medium. The addition of glucose, sucrose, and lactose (10 g/L) enhanced both biomass and carotenoids productivity, with the highest level reaching 4.53 ± 0.32 μg/mL when glucose was added. According to the findings of orthogonal studies based on the OD600 and carotenoids productivity, the best conditions for open fermentation were salinity 20-25%, rotation speed 150-200 rpm, and pH 7.0-8.2. The up-scaled open fermentation was carried out in a 7 L medium under optimum culture conditions. At 96 h, the OD600 and carotenoids productivity were 9.86 ± 0.51 (dry weight 10.40 ± 1.27 g/L) and 7.31 ± 0.65 μg/mL (701.40 ± 21.51 μg/g dry weight, respectively). When amplified with both universal bacterial primer and archaeal primer in the open fermentation, Halorubrum remained the dominating species, indicating that contamination was kept within an acceptable level. To summarize, open fermentation of Halorubrum is a promising method for producing C50 carotenoids.