System Safety is the Systems Engineering (SE) application of engineering and management principles, criteria, and techniques to achieve acceptable risk within the constraints of operational effectiveness and suitability, schedule, and cost throughout the system’s lifecycle. System safety covers the entire spectrum of environment, safety, and occupational health (ESOH) considerations. It is an integral part of the Systems Engineering Process and Risk Management Process and specific activities are required throughout the different Acquisition Phases. 
System Safety Engineering
System Safety Engineering is an engineering discipline that employs specialized knowledge and skills in applying scientific and engineering principles, criteria, and techniques to identify hazards and then to eliminate the hazards or reduce the associated risks when the hazards cannot be eliminated. It defines requirements for design and systems engineering, taking into account the potential risks, Verification and Validation (V&V) of effective mitigation, and residual risk acceptance by certification or approval authorities. It identifies and analyzes behavioral and interface requirements, the design architecture, and the human interface within the context of both systems and systems of systems (SoS). 
The main objective of system safety engineering, which includes software system safety, is the application of engineering and management principles, criteria, and techniques to optimize all aspects of safety within the constraints of operational effectiveness, time, and cost throughout all phases of the system lifecycle.
Program management is ultimately responsible for the development of a safe system. The commitment to provide qualified personnel and an adequate budget and schedule for a software development program begins with the program director or Program Manager (PM). Senior management must be a strong voice of safety advocacy and must communicate this commitment to each level of program and technical management. The PM must provide the necessary resources to support the integrated safety process between systems engineering, software engineering, and safety engineering in the design, development, test, operation, and maintenance of the system software.
Software System Safety
It is essential to perform system safety engineering tasks on safety-critical systems to reduce safety risk in all aspects of a program. These tasks include software system safety activities involving the design, code, test, independent verification and validation (IV&V), operation and maintenance, and change control functions within the software engineering development and deployment processes. 
The purpose of the Handbook above is to provide management and engineering guidelines to achieve a reasonable level of assurance that the software will execute within the system context with an acceptable level of safety risk.
AcqLinks and References:
-  Joint Software Systems Safety Engineering Handbook (JSSSEH) – 27 Aug 2010
-  MIL-STD-882E “Standard Practice for System Safety” – 11 May 2012